Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1995 Mar 14;92(6):2259–2262. doi: 10.1073/pnas.92.6.2259

Specific T-cell tolerance may reflect selective activation of lymphokine synthesis.

L Vidard 1, L J Colarusso 1, B Benacerraf 1
PMCID: PMC42463  PMID: 7892258

Abstract

Selective T-cell unresponsiveness, as measured by interleukin 2 (IL-2) synthesis upon challenge with antigen, was induced in SJL mice by ovalbumin (OVA) in incomplete or complete Freund's adjuvant administered i.p. or s.c. Ten days later, the mice were given booster injections of 100 micrograms of OVA/complete Freund's adjuvant. On day 20, lymph node and spleen cells were challenged in vitro with serial dilutions of OVA. There was an antigen-specific dose-dependent down regulation of IL-2 production and T-cell proliferation in lymph node T cells. Concomitantly, 100 micrograms of OVA up regulated IL-4 and, to a lesser extent, interferon gamma (IFN-gamma) production, particularly by spleen T cells. Altogether, these data indicate that the drop of IL-2 production and T-cell proliferation, as well as the up regulation of IL-4 and IFN-gamma production, are complex manifestations of an evolving T-cell response. The maturation of the T-cell response leads to the production of different patterns of lymphokines, which may be significantly affected, as desired, by dosage, timing, and route of immunization, as well as by the choice of adjuvants.

Full text

PDF
2259

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bradley L. M., Atkins G. G., Swain S. L. Long-term CD4+ memory T cells from the spleen lack MEL-14, the lymph node homing receptor. J Immunol. 1992 Jan 15;148(2):324–331. [PubMed] [Google Scholar]
  2. Bradley L. M., Duncan D. D., Yoshimoto K., Swain S. L. Memory effectors: a potent, IL-4-secreting helper T cell population that develops in vivo after restimulation with antigen. J Immunol. 1993 Apr 15;150(8 Pt 1):3119–3130. [PubMed] [Google Scholar]
  3. Budd R. C., Cerottini J. C., MacDonald H. R. Selectively increased production of interferon-gamma by subsets of Lyt-2+ and L3T4+ T cells identified by expression of Pgp-1. J Immunol. 1987 Jun 1;138(11):3583–3586. [PubMed] [Google Scholar]
  4. Burstein H. J., Abbas A. K. In vivo role of interleukin 4 in T cell tolerance induced by aqueous protein antigen. J Exp Med. 1993 Feb 1;177(2):457–463. doi: 10.1084/jem.177.2.457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cherwinski H. M., Schumacher J. H., Brown K. D., Mosmann T. R. Two types of mouse helper T cell clone. III. Further differences in lymphokine synthesis between Th1 and Th2 clones revealed by RNA hybridization, functionally monospecific bioassays, and monoclonal antibodies. J Exp Med. 1987 Nov 1;166(5):1229–1244. doi: 10.1084/jem.166.5.1229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. De Wit D., Van Mechelen M., Ryelandt M., Figueiredo A. C., Abramowicz D., Goldman M., Bazin H., Urbain J., Leo O. The injection of deaggregated gamma globulins in adult mice induces antigen-specific unresponsiveness of T helper type 1 but not type 2 lymphocytes. J Exp Med. 1992 Jan 1;175(1):9–14. doi: 10.1084/jem.175.1.9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fiorentino D. F., Zlotnik A., Vieira P., Mosmann T. R., Howard M., Moore K. W., O'Garra A. IL-10 acts on the antigen-presenting cell to inhibit cytokine production by Th1 cells. J Immunol. 1991 May 15;146(10):3444–3451. [PubMed] [Google Scholar]
  8. Firestein G. S., Roeder W. D., Laxer J. A., Townsend K. S., Weaver C. T., Hom J. T., Linton J., Torbett B. E., Glasebrook A. L. A new murine CD4+ T cell subset with an unrestricted cytokine profile. J Immunol. 1989 Jul 15;143(2):518–525. [PubMed] [Google Scholar]
  9. Heinzel F. P., Sadick M. D., Holaday B. J., Coffman R. L., Locksley R. M. Reciprocal expression of interferon gamma or interleukin 4 during the resolution or progression of murine leishmaniasis. Evidence for expansion of distinct helper T cell subsets. J Exp Med. 1989 Jan 1;169(1):59–72. doi: 10.1084/jem.169.1.59. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hu-Li J., Ohara J., Watson C., Tsang W., Paul W. E. Derivation of a T cell line that is highly responsive to IL-4 and IL-2 (CT.4R) and of an IL-2 hyporesponsive mutant of that line (CT.4S). J Immunol. 1989 Feb 1;142(3):800–807. [PubMed] [Google Scholar]
  11. Le Gros G., Ben-Sasson S. Z., Seder R., Finkelman F. D., Paul W. E. Generation of interleukin 4 (IL-4)-producing cells in vivo and in vitro: IL-2 and IL-4 are required for in vitro generation of IL-4-producing cells. J Exp Med. 1990 Sep 1;172(3):921–929. doi: 10.1084/jem.172.3.921. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Lin H., Mosmann T. R., Guilbert L., Tuntipopipat S., Wegmann T. G. Synthesis of T helper 2-type cytokines at the maternal-fetal interface. J Immunol. 1993 Nov 1;151(9):4562–4573. [PubMed] [Google Scholar]
  13. Maggi E., Parronchi P., Manetti R., Simonelli C., Piccinni M. P., Rugiu F. S., De Carli M., Ricci M., Romagnani S. Reciprocal regulatory effects of IFN-gamma and IL-4 on the in vitro development of human Th1 and Th2 clones. J Immunol. 1992 Apr 1;148(7):2142–2147. [PubMed] [Google Scholar]
  14. Mosmann T. R., Bond M. W., Coffman R. L., Ohara J., Paul W. E. T-cell and mast cell lines respond to B-cell stimulatory factor 1. Proc Natl Acad Sci U S A. 1986 Aug;83(15):5654–5658. doi: 10.1073/pnas.83.15.5654. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Mosmann T. R., Schumacher J. H., Street N. F., Budd R., O'Garra A., Fong T. A., Bond M. W., Moore K. W., Sher A., Fiorentino D. F. Diversity of cytokine synthesis and function of mouse CD4+ T cells. Immunol Rev. 1991 Oct;123:209–229. doi: 10.1111/j.1600-065x.1991.tb00612.x. [DOI] [PubMed] [Google Scholar]
  16. Naora H., Altin J. G., Young I. G. TCR-dependent and -independent signaling mechanisms differentially regulate lymphokine gene expression in the murine T helper clone D10.G4.1. J Immunol. 1994 Jun 15;152(12):5691–5702. [PubMed] [Google Scholar]
  17. Ohara J., Paul W. E. Production of a monoclonal antibody to and molecular characterization of B-cell stimulatory factor-1. Nature. 1985 May 23;315(6017):333–336. doi: 10.1038/315333a0. [DOI] [PubMed] [Google Scholar]
  18. Pearce E. J., Caspar P., Grzych J. M., Lewis F. A., Sher A. Downregulation of Th1 cytokine production accompanies induction of Th2 responses by a parasitic helminth, Schistosoma mansoni. J Exp Med. 1991 Jan 1;173(1):159–166. doi: 10.1084/jem.173.1.159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Reynolds D. S., Boom W. H., Abbas A. K. Inhibition of B lymphocyte activation by interferon-gamma. J Immunol. 1987 Aug 1;139(3):767–773. [PubMed] [Google Scholar]
  20. Rock K. L. The role of Ia molecules in the activation of T lymphocytes. I. The activation of an IL 1-dependent IL 2-producing T cell hybridoma by Con A requires an interaction, which is not H-2-restricted, with an Ia-bearing accessory cell. J Immunol. 1982 Oct;129(4):1360–1366. [PubMed] [Google Scholar]
  21. Sanders M. E., Makgoba M. W., Sharrow S. O., Stephany D., Springer T. A., Young H. A., Shaw S. Human memory T lymphocytes express increased levels of three cell adhesion molecules (LFA-3, CD2, and LFA-1) and three other molecules (UCHL1, CDw29, and Pgp-1) and have enhanced IFN-gamma production. J Immunol. 1988 Mar 1;140(5):1401–1407. [PubMed] [Google Scholar]
  22. Scott P., Natovitz P., Coffman R. L., Pearce E., Sher A. Immunoregulation of cutaneous leishmaniasis. T cell lines that transfer protective immunity or exacerbation belong to different T helper subsets and respond to distinct parasite antigens. J Exp Med. 1988 Nov 1;168(5):1675–1684. doi: 10.1084/jem.168.5.1675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Street N. E., Schumacher J. H., Fong T. A., Bass H., Fiorentino D. F., Leverah J. A., Mosmann T. R. Heterogeneity of mouse helper T cells. Evidence from bulk cultures and limiting dilution cloning for precursors of Th1 and Th2 cells. J Immunol. 1990 Mar 1;144(5):1629–1639. [PubMed] [Google Scholar]
  24. Swain S. L., Weinberg A. D., English M. CD4+ T cell subsets. Lymphokine secretion of memory cells and of effector cells that develop from precursors in vitro. J Immunol. 1990 Mar 1;144(5):1788–1799. [PubMed] [Google Scholar]
  25. Swain S. L., Weinberg A. D., English M., Huston G. IL-4 directs the development of Th2-like helper effectors. J Immunol. 1990 Dec 1;145(11):3796–3806. [PubMed] [Google Scholar]
  26. Urban J. F., Jr, Madden K. B., Svetić A., Cheever A., Trotta P. P., Gause W. C., Katona I. M., Finkelman F. D. The importance of Th2 cytokines in protective immunity to nematodes. Immunol Rev. 1992 Jun;127:205–220. doi: 10.1111/j.1600-065x.1992.tb01415.x. [DOI] [PubMed] [Google Scholar]
  27. Varner M. W. Autoimmune disorders and pregnancy. Semin Perinatol. 1991 Jun;15(3):238–250. [PubMed] [Google Scholar]
  28. Vidard L., Colarusso L. J., Benacerraf B. Specific T-cell tolerance may be preceded by a primary response. Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5627–5631. doi: 10.1073/pnas.91.12.5627. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. de Waal Malefyt R., Haanen J., Spits H., Roncarolo M. G., te Velde A., Figdor C., Johnson K., Kastelein R., Yssel H., de Vries J. E. Interleukin 10 (IL-10) and viral IL-10 strongly reduce antigen-specific human T cell proliferation by diminishing the antigen-presenting capacity of monocytes via downregulation of class II major histocompatibility complex expression. J Exp Med. 1991 Oct 1;174(4):915–924. doi: 10.1084/jem.174.4.915. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES