Praise for The Interleukin Revolution…
“Smith looks back on his efforts to elucidate the immune system before his rivals beat him to it in this candid memoir.
The author recaps his career, from medical school through a two-decade stint as a medical professor at Dartmouth in the 1970s and 1980s, in which he made pioneering contributions to immunology. The book dives deep into his research on T cells—immune cells that destroy pathogens and provide long-term immunity—and the role of interleukin-2, a protein that promotes T-cell growth. Smith’s narrative features scenes of exhilarating discovery in which experiments worked beautifully and he gradually conceived a vision of interleukins as a set of hormones meticulously regulating the immune system. He twines these with an intimate portrait of cut-throat scientific competition: He recounts how he battled a hidebound immunological establishment, chewed out a journal editor for rejecting a paper, finessed the National Institutes of Health when it dragged its feet renewing his grant, and was backstabbed by a graduate student who stole a cell line his lab developed and sold it for $5,000 to a Japanese company that used it to publish an important finding just before he did (“In science, the only way to maintain one’s sanity and to stay in the game is to always look forward,” he concludes). Smith’s exposition is thorough and comprehensive, and readers see his work develop chronologically, from rudimentary hypotheses and experimentation on mysterious substances to a detailed understanding of molecules and mechanisms. The writing is sophisticated enough for scientists but sufficiently clear and straightforward for interested laypeople to follow, and the author describes lab work in down-to-earth prose that’s full of vivid detail: “I would walk over to the hospital…don my scrubs, and go into the operating room, where the surgeon would drop a tonsil into my cup of saline. Back in the lab…we would slice up the tonsil with a scalpel and forceps, releasing the individual lymphocytes.” The result is a gripping saga of science as a fraught and very human pursuit.
A fascinating look at a life in science, full of “eureka” moments and convoluted power plays.”
– from Kirkus Reviews
Selected Key Publications
The generation of the first antigen-specific functional monoclonal T cells.
1. Gillis, S., and K.A. Smith. Long-term culture of cytotoxic T-lymphocytes. Nature 268:154-156, 1977.
2. Baker, P.E., S. Gillis and K.A. Smith. Monoclonal cytolytic T-cell lines. J. Exp. Med.149:273-278, 1979
The creation of the T cell Growth Factor (IL2) bioassay.
*3. Gillis, S., M.M. Ferm, W. Ou and K.A. Smith. T-cell growth factor: parameters of production and a quantitative microassay for activity. J. Immunol. 120:2027-2032, 1978. * The 2nd most highly cited article in the first 100 years of the Journal of Immunology
The scientific rationale for the interleukin nomenclature.
4. Smith, K.A., K.J. Gilbride, and M.F. Favata. Lymphocyte activating factor promotes T-Cell growth factor production by cloned murine lymphoma cells. Nature 287:853-855, 1980.
5. Smith, K.A., L.B. Lachman, J.J. Oppenheim, and M.F. Favata. The functional relationship of the interleukins. J. Exp. Med. l5l:l55l-l556, 1980
The biochemical characterization of the IL-2 molecule.
6. Robb, R.J., and K.A. Smith. Heterogeneity of human T-Cell growth factor due to glycosylation. Mol. Immunol. 18:1087-1094, 1981.
The generation of the first IL2 monoclonal antibodies and the first purification of IL2 to homogeneity.
7. Smith, K.A., M.F. Favata and S. Oroszlan. Production and characterization of monoclonal antibodies to human interleukin 2: strategy and tactics. J. Immunol. 131:1808-1815, 1983.
The discovery of the IL-2 receptor.
8. Robb, R.J., A. Munck and K.A. Smith. T-cell growth factor receptors: quantitation, specificity and biological relevance. J. Exp. Med. 154:1455-1474, 1981.
The identification of the first IL2 receptor monoclonal antibody and the discovery of the first chain () of the IL-2 receptor.
9. Leonard, W.J., J.M. Depper, T. Uchiyama, K.A. Smith, T.A. Waldmann, and W.C. Greene. A monoclonal antibody, anti-Tac, blocks the membrane binding and action of human T-cell growth factor. Nature 300:267-269, 1982.
The discovery of the second chain () of the IL-2 receptor.
10. Teshigawara, K., H.-M. Wang, K. Kato and K.A. Smith. Interleukin 2 high affinity receptor expression depends on two distinct binding proteins. J. Exp. Med. 165:223-238, 1987.
The first kinetic description of how IL2 receptors bind IL2.
11. Wang, H-M. and K.A. Smith. The interleukin 2 receptor: Functional consequences of its bimolecular structure. J. Exp. Med. 166:1055-1069, 1987.
The discovery of the mechanism of glucocorticoid immunosuppression: inhibition of IL-2 production.
12. Smith, K.A., G.R. Crabtree, S. Kennedy, and A. Munck. Glucocorticoid receptors and glucocorticoid sensitivity of mitogen stimulated and unstimulated human lymphocytes. Nature 267:523-526, 1977.
13. Gillis, S., G.R. Crabtree, and K.A. Smith. Glucocorticoid-induced inhibition of T-cell growth factor production. I. The effect on mitogen-induced lymphocyte proliferation. J. Immunol. 123:1624-1631, 1979.
The demonstration that IL2 promotes T cell cycle progression, not antigen.
14. Cantrell, D.A. and K.A. Smith. The interleukin-2-T cell system: a new cell growth model. Science 224:1312-1316, 1984.
15. Meuer, S.C., R.E. Hussey, D.A. Cantrell, J.C. Hodgdon, S.F. Schlossman, K.A. Smith and E.L. Reinherz. Triggering of the T3-Ti antigen-receptor complex results in clonal T-cell proliferation through an interleukin 2 -dependent autocrine pathway. Proc. Natl. Acad. Sci. USA 81:1509-1513, 1984.
The first description of IL-2-induced gene expression.
16. Stern, J.B. and K.A. Smith. Interleukin 2 induction of T cell G1 progression and c-myb expression. Science 233:203-206, 1986.
The development of new methods to clone and identify novel IL-2-induced genes.
17. Beadling, C., K.W. Johnson, and K.A. Smith. Isolation of interleukin-2-induced immediate-early genes. Proc. Natl. Acad. Sci. U.S.A. 90:2719-2723, 1993.
18. Beadling, C. and Smith,K.A. DNA array analysis of interleukin-2-regulated immediate/early genes. Medical Immunology 1:2, 2002.
The demonstration that memory T cells are differentiated cytokine producing cells.
19. Elhers, S. And K.A. Smith. Differentiation of T cell lymphokine gene expression: The in vitro acquisition of T cell memory. J. Exp. Med., 173:25-36, 1991.
The development of a new nontoxic dosing regimen for IL-2 immunotherapy.
20. Jacobson, E.L., Pilaro, F., and K.A. Smith. Rational IL-2 therapy for HIV- positive individuals: Daily low doses enhance immune function without toxicity.
Proc. Natl. Acad. Sci. U.S.A. 93:10,405-10,410, 1996.
21. Lalezari, J.P., Beal, J.A., Ruane, P.J., Cohen, C. J., Jacobson, E.L., Sundin, D., Leong, W.P., Raffanti, S.P., Wheeler, D.A., Andrson, R.D., Keiser, P., Schrader, S.R., Goodgame, J., Steinhart, C.R., Murphy, R.L., Wolin, M.J., and K.A. Smith. Low dose daily subcutaneous interleukin 2 in combination with highly active anti-retroviral therapy in HIV+ patients: a randomized controlled trial. HIV Clinical Trials 1:1-15, 2000.
22. Smith, K.A., Jacobson, E.L., Sohn, T., Warren, D., Emert, R., and M. Giordano. In vivo assessment of antiviral reactivity in chronic HIV infection. HIV Clinical Trials. 1: 16-22, 2000.
23. Blattman, J.N., Grayson, J.M., Wherry, E.J., Kaech, S.M., Smith, K,A., Ahmed, R. Therapeutic use of IL2 to enhance antiviral T cell responses in vivo. Nature Med. 9:1-8, 2003.
24. Nasca, J., Edghill-Smith, Y., Tsai, W-P., Venzon, D., Tryniszewska, E., hryniewicz, A., moniuszko, M., kinter, A., Smith, K.A., Franchini, G. Contrasting effects of low-dose IL2 on vaccine-boosted Simian Immunodeficiency Virus (SIV)-specific CD4+ and CD8+ T cells in macaques chronically infected with SIVmac251. J Immunol. 174:1913-1921, 2005.
25. Smith, K.A., Andjelic, S., Popmihajlov, Z., Kelly-Rossini, L., Sass, A., Lesser, M., Benkert, S., Waters, C., Ruitenberg, J., and Bellman, P. Immunotherapy with canarypox vaccine and interleukin-2 for HIV infection: Termination of a randomized trial. PLoS Clin Trials. 2007 January; 2(1): e5.
26. West, E.E., Jin, H.T., Rasheed, A.U., Penaloza-Macmaster, P., Ha, S.J., Tan, W.G., Youngblood, B., Freeman, G.J., Smith, K.A., Ahmed, R. PD-L1 blockade synergizes with IL-2 therapy in reinvigorating exhausted T cells. J Clin Invest.123(6):2604-15, 2013.
The demonstration of an IL2-dependent negative feedback loop mediated via FOXP3 that regulates IL2 production
27. Popmihajlov, Z., and K.A. Smith. Negative feedback regulation of T cells via interleukin-2 and FOXP3 reciprocity. PLoS One 2008 February; 3(2): e158
Classics of Immunology Scientific Papers
1798
Jenner, E
An Inquiry into the Causes and Effects of Variolae Vaccinae, a Disease Discovered in Some Western Counties of England. London, Sampson Low; 1798.
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1837
Schwann, T
Preliminary report on experiments concerning alcoholic fermentation and putrefaction.
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1838
Cagnniard-Latour, C.
Memoir on alcoholic fermentation
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Memoir on the alcoholic fermentation.
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Influence of oxygen on the development of yeast and on the alcoholic fermentation. (ABSTRACT)
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1880
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1881
“De l’attenuation des virus et de leur retour a la virulence avec la collaboration de MM Chamberland et Roux”, C. R. Acad. Sci., 28 fevrier 1881, XCII, pp. 429-435.
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1884
Koch, R
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Behring, EA von & Kitasato, S
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1901
Metchnikoff, M
Sur l’Existence de Substances sensibilisatrices Dans La Plupart Des Serums Antimicrobiens
1902
Portier, P & Richet, C
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1903
Arthus, M
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1905
Von Pirquet, C. Frh & Schick, B
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Calmette A, Guerin, C
Vaccination des bovides contre la tuberculose et methode nouvelle de prophylaxie de la tuberculose bovine.
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1931
Shope, R.E.
Swine influenza: I. Experimental transmission and pathology
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1931
Lewis P.A. and Shope, R.E.
Swine influenza. II. A hemophilic bacillus from the respiratory tract of infected swine
J. Exp. Med. 1931 54: 361-371
1933
Smith W, A CH, Laidlaw PP.
A virus obtained from influenza patients.
Lancet. 1933;2:66-8
1935
Landsteiner, K and van der Scheer, J
On Cross Reactions Of Immune Sera To Azoproteins
J Exp Med. 1936;63(3):325-339,
1937
Theiler M, Smith HH
The Use of Yellow Fever Virus Modified by in Vitro Cultivation for Human Immunization.
J Exp Med. 1936; 65: 787-800
1939
Tiselius, A Kabat, E. A.
An Electrophoretic Study of Immune Sera and Purified Antibody Preparations
J Exp Med 65: 119-131
1942
Freund, J & McDermott, K
Sensitization to horse serum by means of adjuvants
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1944
Medawar, P B.
The behaviour and fate of skin autografts and skin homografts in rabbits
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1945
Chase, M
The cellular transfer of cutaneous hypersensitivity to tuberculin
Proc. Soc. Exp. Biol. Med. 59: 134
1945
Owen, RD
Immunogenetic consequences of vascular anastomoses between bovine twins.
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1948
Fagraeus, A
The Plasma Cellular Reaction and its Relation to the Formation of Antibodies In Vitro
J. Immunol. 58:1-13
1952
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Gammaglobulinemia
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1953
Salk, JE
Studies in Human Subjects on Active Immunization Against Poliomyelitis
JAMA 151;1081, 1953
1953
Billingham, Brent & Medawar
‘Actively Acquired Tolerance’ of Foreign Cells
Nature 172: 603
1957
F.M. Burnett
‘A Modification of Jerne’s Theory of Antibody Production Using the Concept of Clonal Selection
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1959
R.R. Porter
‘The Hydrolosis of Rabbit Y-Globulin and Antibodies with Crystalline Papain
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1960
Nowell, Peter, C.
Phytohemagglutinin: An Initiator of Mitosis in Cultures of Normal Human Leukocytes*
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1961
Nowell, Peter C.
Inhibition of Human Leukocyte Mitosis by Prednisolone in Vitro
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1962
Miler J. F.A.P.
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1962
Prof. J. L. Gowans, Dr. D. D. McGregor, Diana M. Cowen, Sir William Dunn & Dr. C. E. FORD
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1963
Jerne NK & Nordin AA
Plaque formation in agar by single antibody-producing cells.
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1963
Kantor FS, Ojeda A, Benacerraf B:
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1965
Cooper, M.D., Peterson, R.D.A., Good, R.A.
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1965
Kasakura S & Lowenstein L
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1965
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A Lymphocyte-Stimulating Factor Produced In Vitro
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1965
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1966
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1966
Schlossman S, Ben-Efraim S, Yaron A, Sober H
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1967
Ishizaka, K & Ishizaka T
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1967
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1967
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1968
Brunner KT, Mauel J, Cerottini JC, Chapuis B.
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1968
McDevitt HO, Tyan ML
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1968
Unanue E, Askonas BA
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McDevitt HO, Chinitz A
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1970
M. C. Raff AND H. H. Wortis
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1970
M. C. Raff, M. Sternberg, R. B. Taylor
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1970
Martin C. Raff
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1970
Benvenuto Pernis, M.D., Luciana Forni, Andluisa Amante
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1970
Annelise Schimpl, Eberhard Wecker
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1970
Fritz H. Bach, Barbara J. Alter, Susan Solliday, David C. Zoschke & Martin Janis
Lymphocyte Reactivity in Vitro – II. Soluble Reconstituting Factor Permitting Response of Purified Lymphocytes
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1971
Hoffman, M & Dutton, RW
Immune Response Restoration with Macrophage Culture Supernatants
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1972
Gery, Igal, Gershon, Richard K., & Waksman, Byron H.
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1972
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1972
Schimpl, A. & Wecker, E.
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1972
Wagner, H and Feldmann, M
Cell-mediated immune response in vitro , : I. A new in vitro system for the generation of cell-mediated cytotoxic activity
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1973
Katz DH, Hamaoka T, Dorf ME, Benacerraf B.
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1973
Rosenthal A, Shevach E
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1973
Shevach E, Rosenthal A
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1973
Steinman RM, Cohn ZA
Identification of a novel cell type in peripheral lymphoid organs of mice. I. Morphology, quantitation, tissue distribution.
J Exp Med. 1973 May 1;137(5):1142-62.
1974
Lindahl P, Leary P, Gresser I
Enhancement of the expression of histocompatibility antigens of mouse lymphoid cells by interferon in vitro
Eur. J. of Immunology Volume 4, Issue 12, 1974. Pages 779-784
1974
Macdonald HR, Engers HD, Cerottini JC, Brunner KT.
Generation of Cytotoxic T Lymphocytes in Vitro. II. Effect of Repeated Exposure to Alloantigens on the Cytotoxic Activity of Long-Term Mixed Leukocyte Cultures.
J Exp Med. 1974 Sep 1;140(3):718-30
1974
Zinkernagel RM, Doherty PC
Restriction of in vitro T cell-mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic or semiallogeneic system.
Nature. 1974 Apr 19;248(450):701-2.
1975
Ben-Sasson SZ, Paul WE, Shevach EM, Green I.
In Vitro Selection and Extended Culture of Antigen-Specific T Lymphocytes. I. Description of Selection Culture Procedure and Initial Characterization of Selected Cells.
J Exp Med. 1975 Jul 1;142(1):90-105.
1975
Herberman RB, Nunn ME, Holden HT, Lavrin DH
Natural cytotoxic reactivity of mouse lymphoid cells against syngeneic and allogeneic tumors. II. Characterization of effector cells.
Int J Cancer 1975, 16:230-239
1975
Kiessling R, Klein E, Wigzell H
Natural killer cells in the mouse. I. Cytotoxic cells with specificity for mouse Moloney leukemia cells. Specificity and distribution according to genotype
Eur J Immunol 1975, 5:112-116
1975
Kisielow P, Hirst JA, Shiku H, Beverley PC, Hoffman MK, Boyse EA, Oettgen HF.
Ly antigens as markers for functionally distinct subpopulations of thymus-derived lymphocytes of the mouse
Nature. 1975 Jan 17;253(5488):219-20
1975
Kohler G, Milstein C
Continuous culture of fused cells secreting antibody of predefined specificity.
Nature 1975, 256:495-499
1975
Svedmyr E.
Long-Term Maintenance In Vitro of Human T Cells by Repeated Exposure to the Same Stimulator Cells Differences When Using Repeated Stimulation in Allogeneic Mixed Leukocyte Culture and When Using Stimulation with Autologous Lymphoblastoid Cells.
Scand J Immunol. 1975 Sep;4(5-6):421-7.
1975
E. A. Carswell, L. J. Old, R. L. Kassel, S. Green, N. Fiore, AND B. Williamson
An endotoxin-induced serum factor that causes necrosis of tumors (activated macrophage)
Proc. Nat. Acad. Sci. USA, Vol. 72, No. 9, pp. 3666-3670, September 1975, Immunology
1976
Dennert G, De Rose M.
Continuously Proliferating T Killer Cells Specific for H-2b Targets: Selection and Characterization.
J Immunol. 1976 Jun;116(6):1601-6.
1976
Green S, Dobrjansky A, Carswell EA, Kassel RL, Old LJ, Fiore N, & Schwartz, MK
Partial Purification of a Serum Factor that Causes Necrosis of Tumors
PNAS 1976 73: 381-385
1976
Hozumi N, Tonegawa S:
Evidence for somatic rearrangement of immunoglobulin genes coding for variable and constant regions.
Proc Natl Acad Sci U S A 1976, 73:3628-3632
1976
Lindahl P, Gresser I, Leary P, Tovey M.
Enhanced Expression of Histocompatibility Antigens of Lymphoid Cells in Mice Treated with Interferon.
J Infect Dis. 1976 Jun;133 Suppl:A66-8
1976
Morgan DA, Ruscetti FW, Gallo R
Selective in vitro growth of T lymphocytes from normal human bone marrow.
Science 1976, 193:1007-1008.
1976
Plate JM
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1977
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J Biol Chem 1977, 252:1998-2003
1977
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Long Term Culture of Tumour-Specific Cytotoxic T Cells
Nature 1977, 268:154-156
1977
Tonegawa S, Brack C, Hozumi N, Schuller R
Cloning of an immunoglobulin variable region gene from mouse embryo
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1978
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Cell 1978, 15:1133-1139
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T Cell Growth Factor: Parameters of Production and a Quantitative Microassay for Activity
J Immunol. 1978 Jun;120(6):2027-32.
1978
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J Exp Med. 1978 Oct 1;148(4):1093-8.
1978
Seidman J, Edgell M, Leder P
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Nature 1978, 271:582-586
1979
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J Exp Med. 1979 Jan 1;149(1):273-8.
1979
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J Immunol. 1979 Oct;123(4):1632-8
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Eur. J. Immunol. 1980.10: 758-762
1980
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Nature. 1980 Sep 4;287(5777):47-9
1980
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Nature. 1980 Oct 30;287(5785):853-5
1980
Smith KA, Lachman LB. Oppenheim, JJ and Favata, MF
The Functional Relationship of the Interleukins
J Exp Med. 1980 Jun 1;151(6):1551-6.
1981
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Eur J Immunol 1981, 11:657-661
1981
Robb RJ, Munck A, Smith KA.
T Cell Growth Factor Receptors. Quantitation, Specificity, and Biological Relevance
J Exp Med. 1981 Nov 1;154(5):1455-74.
1981
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Mol Immunol. 1981 Dec;18(12):1087-1094
1982
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J Exp Med 1982, 155:734-748
1982
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Identification of a T cell-derived B cell growth factor distinct from interleukin 2.
J Exp Med 1982, 155:914-923
1982
Leonard WJ, Depper JM, Uchiyama T, Smith KA, Waldmann TA, Greene WC.
A monoclonal antibody that appears to recognize the receptor for human T-cell growth factor; partial characterization of the receptor.
Nature. 1982 Nov 18;300(5889):267-9.
1982
Stefan C. Meuer, Stuart F. Schlossman, AND Ellis L. Reinherz
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1983
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J. Exp. Med. 1983 157: 1149-1169
1983
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Cell 1983, 34:739-746.
1983
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Clonotypic Structures Involved in Antigen-Specific Human T Cell Function. Relationship to the T3 Molecular Complex
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1983
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Antigen-Like Effects of Monoclonal Antibodies Directed at Receptors on Human T Cell Clones
J. Exp. Med. 1983 158: 988-993
1983
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J Immunol 1983, 131:826-832
1983
Smith KA, Favata MF and Oroszlan, S
Production and Characterization of Monoclonal Antibodies to Human Interleukin 2: Strategy and Tactics
J Immunol. 1983 Oct;131(4):1808-15
1983
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Nature. 1983 Mar 24-30;302(5906):305-10.
1983
Stefan C. Meuer, Oreste Acuto, Rebecca E. Hussey, James C. Hodgdon, Kathleen A. Fitzgerald, Stuart F. Schlossman & Ellis L. Reinherz
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Nature, Vol. 303, 30 June 1983
1983
STEFAN C. MEUER,* JAMES C. HODGDON, REBECCA E. HUSSEY, JEFFREY P. PROTENTIS, STUART F. SCHLOSSMAN, AND ELLIS L. REINHERZ
ANTIGEN-LIKE EFFECTS OF MONOCLONAL ANTIBODIES DIRECTED AT RECEPTORS ON HUMAN T CELL CLONES*
JEM 158-988, 1983
1983
ORESTE ACUTO,* STEFAN C. MEUER, JAMES C. HODGDON, STUART F. SCHLOSSMAN, AND ELLIS L. REINHERZ
PEPTIDE VARIABILITY EXISTS WITHIN 𝝰 AND 𝝱 SUBUNITS OF THE T CELL RECEPTOR FOR ANTIGEN
JEM 158-1368, 1983
1983
Oreste Acute, Rebecca E. Hussey, Kathleen A. Fitzgerald, Jeffrey P. Protentis, Stefan C. Meuer, Stuart F. Schlossman, and Ellis L. Reinherz
The Human T Cell Receptor: Appearance in Ontogeny and Biochemical Relationship of 𝝰 and 𝝱 Subunits on IL-2 Dependent Clones and T Cell Tumors
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The Interleukin-2 T-Cell System: A New Cell Growth Model
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Isolation of cDNA Clones Encoding T Cell-Specific Membrane-Associated Proteins
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PHILIP E. AURON, ANDREW C. WEBB, LANNY J. ROSENWASSER, STEVEN F. MUCCI,
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Nucleotide sequence of human monocyte interleukin 1
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Proc. Nati. Acad. Sci. USA, Vol. 81, pp. 7907-7911, December 1984
1984
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T-cell growth factor: complete nucleotide sequence and organization of the gene in normal and malignant cells.
Proc Natl Acad Sci U S A. 1984 March; 81(6): 1634-1638
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1985
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Purification of cachectin, a lipoprotein lipase-suppressing hormone secreted by endotoxin-induced RAW 264.7 cells.
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Purification to homogeneity and characterization of human B-cell differentiation factor (BCDF or BSFp-2).
Proc Natl Acad Sci U S A 1985, 82:5490-5494.
1985
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Purification and physicochemical characterization of murine T cell replacing factor (TRF)
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Inducibility of ? immunoglobulin enhancer-binding protein NF-?B by a posttranslational mechanism
Cell, Vol 47, 921-928, 26 December 1986
1986
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Interleukin-2 Induction of T-Cell G1 Progression and c-myb Expression
Science, Volume 233, Issue 4760, pp. 203-206
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Complementary DNA for a novel human Interleukin (BSF-2) that induces B lymphocytes to produce immunoglobulin
Nature Vol. 324 6 November 1986
1986
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Cloning of complementary DNA encoding T-cell replacing factor and identity with B-cell growth factor II
Nature Vol. 324 6 November 1986
1986
Yoshihiko Noma, Paschalis Sideras, Takayuki Naito, Susanne Bergstedt-Lindquist, Chihiro Azuma, Eva Severinson, Toshizumi Tanabe, Tatsuo Kinashi, Fumihiko Matsuda, Yoshio Yaoita & Tasuku Honjo
Cloning of cDNA encoding the murine IgGl induction factor by a novel strategy using SP6 promoter
Nature Vol. 319 20 February 1986
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Structure of the human class I Histocompatibility Antigen, HLA-A2
Nature. 1987 Oct 8-14;329(6139):506-12
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The foreign antigen binding site and T cell recognition regions of class I histocompatibility antigens.
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1987
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A new T-cell receptor gene located within the alpha locus and expressed early in T-cell differentiation.
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Antigen Presentation by Chemically Modified Splenocytes Induces Antigen-Specific T cell Unresponsiveness in Vitro and in Vivo
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T cell tolerance by clonal elimination in the thymus
Cell. 1987 Apr 24;49(2):273-80.
1987
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Identification and sequence of a fourth human T cell antigen receptor chain.
Nature. 1987 Dec 10-16;330(6148):569-72.
1987
Teshigawara K, Wang HM, Kato K, Smith KA.
Interleukin 2 high-affinity receptor expression requires two distinct binding proteins
J Exp Med. 1987 Jan 1;165(1):223-38.
1987
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The interleukin 2 receptor. Functional consequences of its bimolecular structure.
J Exp Med. 1987 Oct 1;166(4):1055-69
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Positive Selection of Antigen-specific T cells in Thymus by Restricting MHC Molecules.
Nature. 1988 Oct 20;335(6192):730-3
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Tolerance in T-Cell-Receptor Transgenic Mice Involves Deletion of Nonmature CD4+8+ Thymocytes.
Nature. 1988 Jun 23;333(6175):742-6.
1988
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B cell precursor growth-promoting activity. Purification and characterization of a growth factor active on lymphocyte precursors.
J Exp Med 1988, 167:988-1002
1988
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Identification of a Putative Regulator of Early T Cell Activation Genes
Science 1988 Jul 8;241(4862):202-5
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Interleukin-2: inception, impact, and implications.
Science. 1988 May 27;240(4856):1169-76.
1988
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Thymic major histocompatibility complex antigens and the alpha beta T-cell receptor determine the CD4/CD8 phenotype of T cells.
Nature. 1988 Sep 15;335(6187):229-33.
1989
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Inhibitory effect of TNF alpha antibodies on synovial cell interleukin-1 production in rheumatoid arthritis.
The Lancet 1989, 2:244-247.
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CD28 activation pathway regulates the production of multiple T-cell-derived lymphokines/cytokines.
Proc Natl Acad Sci U S A. 1989 Feb;86(4):1333-7.
1989
Tullia Lindsten, Carl H. June, Jeffrey A. Ledbetter, Gregory Stella and Craig B. Thompson
Regulation of Lymphokine Messenger RNA Stability by a Surface-Mediated T Cell Activation Pathway
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ISGF3, the transcriptional activator induced by interferon alpha, consists of multiple interacting polypeptide chains
Proc Natl Acad Sci U S A. 1990 Nov;87(21):8555-9.
1990
Le Gros G, Ben-Sasson SZ, Seder R, Finkelman FD, Paul WE
Generation of interleukin 4 (IL4)-producing cells in vivo and in vitro: IL2 and IL4 are required for in vitro generation of IL4-producing cells
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RAG-1 and RAG-2, Adjacent Genes That Synergistically Activate V(D)J Recombination
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1991
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Induction of interferon gamma production by natural killer cell stimulatory factor: characterization of the responder cell and synergy with other inducers.
J Exp Med 1991, 173:869-879
1991
Ehlers S, Smith KA.
Differentiation of T cell lymphokine gene expression: the in vitro acquisition of T cell memory.
J Exp Med. 1991 Jan 1;173(1):25-36.
1991
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Isolation and expression of human cytokine synthesis inhibitory factor cDNA clones: Homology to Epstein-Barr virus open reading frame BCRF1.
Proc Natl Acad Sci U S A 1991, 88:1172-1176.
1991
Zmuidzinas A, Mamon HJ, Roberts TM, Smith KA.
Interleukin-2-triggered Raf-1 expression, phosphorylation, and associated kinase activity increase through G1 and S in CD3-stimulated primary human T cells
Mol Cell Biol. 1991 May;11(5):2794-803
1992
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Unraveling the structure of IL-2.
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1992
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1992
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Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death.
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Identification of a Novel Surface Protein on Activated CD4+ T Cells that Induces Contact-Dependent B Cell Differentiation (Help).
J Exp Med. 1992 Apr 1;175(4):1091-101
1992
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A 39-kDa protein on activated helper T cells binds CD40 and transduces the signal for cognate activation of B cells.
Proc Natl Acad Sci U S A. 1992 Jul 15;89(14):6550-4.
1992
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An associated molecule, p64, with IL-2 receptor beta chain. Its possible involvement in the formation of the functional intermediate-affinity IL-2 receptor complex.
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1992
Toshikazu Takeshita, Hironobu Asao, Kiyoshi Ohtani, Naoto Ishii, Satoru Kumaki, Nobuyuki Tanaka, Hiroshi Munakata, Masataka Nakamura and Kazuo Sugamura
Cloning of the γ Chain of the Human IL-2 Receptor
Science , Jul. 17, 1992, New Series, Vol. 257, No. 5068 (Jul. 17, 1992), pp. 379-382
1992
Williams R, Feldmann M, Maini R
Anti-tumor necrosis factor ameliorates joint disease in murine collagen-induced arthritis.
Proc Natl Acad Sci U S A 1992, 89:9784-9788
1993
Beadling C, Johnson KW, Smith KA
Isolation of interleukin 2-induced immediate-early genes
Proc Natl Acad Sci U S A 1993, 90:2719-2723
1993
Fuleihan R, Ramesh N, Loh R, Jabara H, Rosen R, Chatila T, Fu S, Stamenkovic I, Geha R
Defective expression of the CD40 ligand in X chromosome-linked immunoglobulin deficiency with normal or elevated IgM.
Proc Natl Acad Sci U S A 1993, 90:2170-2173
1993
Ghosh P, Tan T, Rice NR, Sica A, Young HA
The interleukin 2 CD28-responsive complex contains at least three members of the NF-kB family: c-Rel, p50, and p65.
Proceedings of the National Academy of Sciences USA 1993, 90:1696-1700.
1993
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Dendritic cells and macrophages are required for Th1 development of CD4+ T cells from alpha beta TCR transgenic mice IL-12 substitution for macrophages to stimulate IFN-gamma production is IFN-gamma-dependent.
Int Immunol 1993, 5:1119-1128
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Isolation of the cyclosporin-sensitive T cell transcription factor NFATp.
Science. 1993 Oct 29;262(5134):750-4.
1993
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Virus Persistence in Acutely Infected Immunocompetent Mice by Exhaustion of Antiviral Cytotoxic Effector T Cells
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1993
Noguchi M, Yi H, Rosenblatt HM, Filipovich AH, Adelstein S, Modi WS, McBride OW, Leonard WJ
Interleukin 2 receptor gamma chain mutation results in X-linked severe combined immunodeficiency in humans.
Cell 1993, 73:147-157
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IL-2-dependent induction of G1 cyclins in primary T cells is not blocked by rapamycin or cyclosporin A.
Int Immunol. 1993 Oct;5(10):1199-209.
1994
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Activation of JAK kinases and STAT proteins by interleukin-2 and interferon alpha, but not the T cell antigen receptor, in human T lymphocytes
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1994
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J Exp Med 1994, 180:1251-1262
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Burton J, Bamford R, Peters C, Grant A, Kurys G, Goldman C, Brennan J, Roessler E, Waldmann T
A lymphokine, provisionally designated interleukin T and produced by a humanadult T-cell leukemia line, stimulates T-cell proliferation and the induction of lymphokine-activated killer cells.
Proc Natl Acad Sci U S A 1994, 91:4935-4939
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Jak-STAT Pathways and Transcriptional Activation in Response to IFNs and Other Extracellular Signaling Proteins
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Cloning of a T cell growth factor that interacts with the beta chain of the interleukin-2 receptor.
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Antigen-specific human monoclonal antibodies from mice engineered with human Ig heavy and light chain YACS
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Phosphorylation and activation of the Jak-3 Janus kinase in response to interleukin-2.
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Interleukin-2-mediated elimination of the p27Kip1 cyclin-dependent kinase inhibitor prevented by rapamycin.
Nature. 1994 Dec 8;372(6506):570-3.
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Efficient Presentation of Soluble Antigen by Cultured Human Dendritic Cells is Maintained by Granulocyte/Macrophage Colony-Stimulating Factor plus Interleukin 4 and Downregulated by Tumor Necrosis Factor Alpha
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Fc Receptors Initiate the Arthus Reaction: Redefining the Inflammatory Cascade
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