Single cell analysis reveals regulated hierarchical T cell antigen receptor signaling thresholds and intraclonal heterogeneity for individual cytokine responses of CD4+ T cells

Journal of Experimental Medicine

Volumn 186, Issue 5, 1997, Pages 757-766

  Itoh, Yasushi ^a   Germain, Ronald N ^a  

^a NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CD4 ANTIGEN; CYTOKINE; GAMMA INTERFERON; INTERLEUKIN 2; T LYMPHOCYTE RECEPTOR;

ANIMAL CELL; ARTICLE; CELLULAR IMMUNITY; CONTROLLED STUDY; HELPER CELL; LYMPHOCYTE FUNCTION; MOUSE; NONHUMAN; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; T LYMPHOCYTE SUBPOPULATION;

AMINO ACID SEQUENCE; ANIMALS; ANTIGEN PRESENTATION; ANTIGENS, CD; CLONE CELLS; COCULTURE TECHNIQUES; DOWN-REGULATION; ENZYME-LINKED IMMUNOSORBENT ASSAY; GENE EXPRESSION REGULATION; INTERFERON TYPE II; INTERLEUKIN-2; INTERLEUKIN-3; LIGANDS; LYMPHOCYTE ACTIVATION; MAJOR HISTOCOMPATIBILITY COMPLEX; MICE; MOLECULAR SEQUENCE DATA; PEPTIDE FRAGMENTS; RECEPTORS, ANTIGEN, T-CELL; RNA, MESSENGER; SIGNAL TRANSDUCTION; TH1 CELLS;

EID: 0030846262     PISSN: 00221007     EISSN: None     Source Type: Journal    
DOI: 10.1084/jem.186.5.757     Document Type: Article

References (48)

1. Paul, W.E., and R.A. Seder. 1994. Lymphocyte responses and cytokines. Cell. 76:241-251.
2. Janeway, C.A., Jr., and K. Bottomly. 1994. Signals and signs for lymphocyte responses. Cell. 76:275-285.
3. + T cells. Annu. Rev. Immunol. 12:635-673.
4. Schwartz, R.H. 1996. Models of T cell anergy: is there a common molecular mechanism? J. Exp. Med. 184:1-8.
5. Parish, C.R. 1971. Immune response to chemically modified flagellin. II. Evidence for a fundamental relationship between humoral and cell-mediated immunity. J. Exp. Med. 134:21-47.
6. Bretscher, P.A., G.J. Wei, J.N. Menon, and H. Bielefeldt-Ohmann. 1992. Establishment of stable, cell-mediated immunity that makes "susceptible" mice resistant to Leishmania major. Science (Wash. DC). 257:539-542.
7. + T helper cell phenotype development in a T cell receptor-αβ transgenic model. J. Exp. Med. 182:1579-1584.
8. + T cells. J. Exp. Med. 182:1591-1596.
9. Racioppi, L., F. Ronchese, L.A. Matis, and R.N. Germain. 1993. Peptide-major histocompatibility complex class II complexes with mixed agonist/antagonist properties provide evidence for ligand-related differences in T cell receptor-dependent intracellular signaling. J. Exp. Med. 177:1047-1060.
10. Valitutti, S., S. Müller, M. Dessing, and A. Lanzavecchia. 1996. Different responses are elicited in cytotoxic T lymphocytes by different levels of T cell receptor occupancy. J. Exp. Med. 183:1917-1921.
11. Viola, A., and A. Lanzavecchia. 1996. T cell activation determined by T cell receptor number and tunable threshold. Science (Wash. DC). 273:104-106.
12. Schwartz, R.H. 1992. Costimulation of T lymphocytes: the role of CD28, CTLA-4, and B7/BB1 in interleukin-2 production and immunotherapy. Cell. 71:1065-1068.
13. Linsley, P.S., and J.A. Ledbetter. 1993. The role of the CD28 receptor during T cell responses to antigen. Annu. Rev. Immunol. 11:191-212.
14. Fiering, S., J.P. Northrop, G.P. Nolan, P.S. Mattila, G.R. Crabtree, and L.A. Herzenberg. 1990. Single cell assay of a transcription factor reveals a threshold in transcription activated by signals emanating from the T cell antigen receptor. Genes Dev. 4:1823-1834.
15. Karttunen, J., and N. Shastri. 1991. Measurement of ligand-induced activation in single viable T cells using the lacZ reporter gene. Proc. Natl. Acad. Sci. USA. 88:3972-3976.
16. Reinherz, E.L., S. Meuer, K.A. Fitzgerald, R.E. Hussey, H. Levine, and S.F. Schlossman. 1982. Antigen recognition by human T lymphocytes is linked to surface expression of the T3 molecular complex. Cell. 30:735-743.
17. Saito, T., A. Weiss, J. Miller, M.A. Norcross, and R.N. Germain. 1987. Specific antigen Ia activation of transfected human T cells expressing murine Ti αβ-human T3 receptor complexes. Nature (Lond.). 325:125-130.
18. Valitutti, S., S. Müller, E. Cella, E. Padovan, and A. Lanzavecchia. 1995. Serial triggering of many T cell receptors by a few peptide-MHC complexes. Nature (Lond.). 375:148-151.
19. Boyer, C., N. Auphan, J. Gabert, D. Blanc, B. Malissen, and A.M. Schmitt-Verhulst. 1989. Comparison of phosphorylation and internalization of the antigen receptor/CD3 complex, CD8, and class I MHC-encoded proteins on T cells. Role of intracytoplasmic domains analyzed with hybrid CD8/class I molecules. J. Immunol. 143:1905-1914.
20. Luton, F., M. Buferne, J. Davoust, A.M. Schmitt-Verhulst, and C. Boyer. 1994. Evidence for protein tyrosine kinase involvement in ligand-induced TCR/CD3 internalization and surface redistribution. J. Immunol. 153:63-72.
21. Lee, C.L.Y., S.H.S. Lee, F.T. Jay, and K.R. Rozee. 1990. Immunobiological study of interferon-gamma-producing cells after staphylococcal enterotoxin B stimulation. Immunology. 70:94-99.
22. Kuchroo, V.K., M. Prabhu Das, J.A. Brown, A.M. Ranger, S.S. Zamvil, R.A. Sobel, H.L. Weiner, N. Nabavi, and L.H. Glimcher. 1995. B7-1 and B7-2 costimulatory molecules activate differentially the Th1/Th2 developmental pathways: application to autoimmune disease therapy. Cell. 80:707-718.
23. Freeman, G.J., V.A. Boussiotis, A. Anumanthan, G.M. Bernstein, X.Y. Ke, P.D. Rennert, G.S. Gray, J.G. Gribben, and L.M. Nadler. 1995. B7-1 and B7-2 do not deliver identical costimulatory signals, since B7-2 but not B7-1 preferentially costimulates the initial production of IL-4. Immunity. 2:523-532.
24. + T cells and induces synthesis of IL-3 and IFN-γ but not IL-4 or IL-6. Int. Immunol. 4:475-485.
25. Bucy, R.P., A. Panoskaltsis-Mortari, G.Q. Huang, J. Li, L. Karr, M. Ross, J.H. Russell, K.M. Murphy, and C.T. Weaver. 1994. Heterogeneity of single cell cytokine gene expression in clonal T cell populations. J. Exp. Med. 180:1251-1262.
26. + T cells activated in a T helper type 2-like response in vivo. Eur. J. Immunol. 25:1168-1175.
27. + T cell phenotype development. Proc. Natl. Acad. Sci. USA. 92: 7565-7569.
28. Hecht, T.T., D.L. Longo, and L.A. Matis. 1983. The relationship between immune interferon production and proliferation in antigen-specific, MHC-restricted T cell lines and clones. J. Immunol. 131:1049-1055.
29. Ding, L., P.S. Linsley, L.-Y. Huang, R.N. Germain, and E.M. Shevach. 1993. IL-10 inhibits macrophage costimulatory activity by selectively inhibiting the up-regulation of B7 expression. J. Immunol. 151:1224-1234.
30. Muraille, E., G. De Becker, M. Bakkus, K. Thielemans, J. Urbain, M. Moser, and O. Leo. 1995. Co-stimulation lowers the threshold for activation of naive T cells by bacterial superantigens. Int. Immunol. 7:295-304.
31. Madrenas, J., R.H. Schwartz, and R.N. Germain. 1996. Interleukin 2 production, not the pattern of early T cell antigen receptor-dependent tyrosine phosphorylation, controls anergy induction by both agonists and partial agonists. Proc. Natl. Acad. Sci. USA. 93:9736-9741.
32. + T cells. Science (Wash. DC). 271: 1272-1276.
33. + T cells. Science (Wash. DC). 271:1276-1278.
34. Glimcher, L.H., and C.J. Kara. 1992. Sequences and factors: a guide to MHC class-II transcription. Annu. Rev. Immunol. 10: 13-49.
35. Chang, C.-H., and R.A. Flavell. 1995. Class II transactivator regulates the expression of multiple genes involved in antigen presentation. J. Exp. Med. 181:765-767.
36. Jiang, J., and M. Levine. 1993. Binding affinities and cooperative interactions with bHLH activators delimit threshold responses to the dorsal gradient morphogen. Cell. 72:741-752.
37. Chung, J.D., G. Stephanopoulos, K. Ireton, and A.D. Grossman. 1994. Gene expression in single cells of Bacillus subtilis: evidence that a threshold mechanism controls the initiation of sporulation. J. Bacteriol. 176:1977-1984.
38. Garrity, P.A., D. Chen, E.V. Rothenberg, and B.J. Wold. 1994. Interleukin-2 transcription is regulated in vivo at the level of coordinated binding of both constitutive and regulated factors. Mol. Cell. Biol. 14:2159-2169.
39. Chen, D., and E.V. Rothenberg. 1994. Interleukin 2 transcription factors as molecular target of cAMP inhibition: delayed inhibition kinetics and combinational transcription roles. J. Exp. Med. 179:931-942.
40. Tanaka, N., and T. Taniguchi. 1992. Cytokine gene regulation: regulatory cis-elements and DNA binding factors involved in the interferon system. Adv. Immunol. 52:263-281.
41. Howard, M.C., A. Miyajima, and R. Coffman. 1993. T cell-derived cytokines and their receptors. In Fundamental Immunology. W.E. Paul, editor. Raven Press, New York. 763-800.
42. Rao, A. 1994. NF-ATp: a transcription factor required for the co-ordinate induction of several cytokine genes. Immunol. Today. 15:274-281.
43. Sloan-Lancaster, J., A.S. Shaw, J.B. Rothbard, and P.M. Allen. 1994. Partial T cell signaling: altered phospho-ζ and lack of Zap70 recruitment in APL-induced T cell anergy. Cell. 79:913-922.
44. Madrenas, J., R.L. Wange, J.L. Wang, N. Isakov, L.E. Samelson, and R.N. Germain. 1995. ζ phosphorylation without ZAP-70 activation induced by TCR antagonists or partial agonists. Science (Wash. DC). 267:515-518.
45. Evavold, B.D., and P.M. Allen. 1991. Separation of IL-4 production from Th cell proliferation by an altered T cell receptor ligand. Science (Wash. DC). 252:1308-1310.
46. Hogquist, K.A., S.C. Jameson, W.R. Heath, J.L. Howard, M.J. Bevan, and F.R. Carbone. 1994. T cell receptor antagonist peptides induce positive selection. Cell. 76:17-27.
47. Jameson, S.C., K.A. Hogquist, and M.J. Bevan. 1994. Specificity and flexibility in thymic selection. Nature (Lond.). 369: 750-752.
48. + T cells. Immunity. 3:79-86.