Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1983 Jun 1;157(6):1867–1884. doi: 10.1084/jem.157.6.1867

T cell regulation of B cell activation. I-A-restricted T suppressor cells inhibit the major histocompatibility complex-restricted interactions of T helper cells with B cells and accessory cells

PMCID: PMC2187040  PMID: 6189950

Abstract

The present studies were carried out to characterize the cellular interactions involved in the activation and function of the antigen- specific and antigen-nonspecific T suppressor (Ts) cells that regulate the IgG responses of Lyb-5-B cells. The in vitro activation of both Lyt- 1+2- antigen-nonspecific Ts cells and Lyt-1-2+ antigen-specific Ts cells was shown to require the interaction of accessory cells and antigen-primed T cells. It was further demonstrated that this interaction was major histocompatibility complex (MHC)-restricted in that T cell recognition of I-A-encoded determinants on accessory cells was required for Ts cell activation. The activation of antigen-primed (A X B)F1 T cells with antigen in the presence of parentA or parentB accessory cells resulted, respectively, in the generation of parentA- restricted or parentB-restricted Ts cells. ParentA-restricted F1 Ts cells suppressed the responses generated by (A X B)F1 T helper (Th) cells cooperating with parentA (B + accessory) cells but did not suppress responses by the same (A X B)F1 Th cell population cooperating with parentB (B + accessory) cells. Neither parentA-restricted Ts cells alone nor parentB-restricted Ts cells alone suppressed the responses of (A X B)F1 (B + accessory) cells, whereas a mixture of these two Ts cell populations was able to significantly suppress the responses of F1 (B + accessory) cells. In contrast, responses of (A X B)F1 leads to parentA Th cells (restricted to recognizing parentA but not parentB MHC determinants on F1 cells) and (A X B)F1 (B + accessory) cells was suppressed by parentA-restricted Ts cells but not by parentB-restricted Ts cells. Collectively these findings suggest that the Ts cell populations characterized here do not function by directly inhibiting the activity of Th cells, B cells or accessory cells of a given MHC genotype, but rather that they appear to function through a unique mechanism involving highly specific inhibition of the interaction between MHC-restricted Th cells and the (B + accessory) cells required for these responses.

Full Text

The Full Text of this article is available as a PDF (1.1 MB).

Selected References

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

  1. Adorini L., Harvey M. A., Miller A., Sercarz E. E. Fine specificity of regulatory T cells. II. Suppressor and helper T cells are induced by different regions of hen egg-white lysozyme in a genetically nonresponder mouse strain. J Exp Med. 1979 Aug 1;150(2):293–306. doi: 10.1084/jem.150.2.293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Asano Y., Hodes R. J. T cell regulation of B cell activation. T cells independently regulate the responses mediated by distinct B cell subpopulations. J Exp Med. 1982 May 1;155(5):1267–1276. doi: 10.1084/jem.155.5.1267. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Asano Y., Shigeta M., Fathman C. G., Singer A., Hodes R. J. Role of the major histocompatibility complex in T cell activation of B cell subpopulations. A single monoclonal T helper cell population activates different B cell subpopulations by distinct pathways. J Exp Med. 1982 Aug 1;156(2):350–360. doi: 10.1084/jem.156.2.350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Asano Y., Singer A., Hodes R. J. Role of the major histocompatibility complex in T cell activation of B cell subpopulations. Major histocompatibility complex-restricted and -unrestricted B cell responses are mediated by distinct B cell subpopulations. J Exp Med. 1981 Oct 1;154(4):1100–1115. doi: 10.1084/jem.154.4.1100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Baxevanis C. N., Ishii N., Nagy Z. A., Klein J. H-2-controlled suppression of T cell response to lactate dehydrogenase B. Characterization of the lactate dehydrogenase B suppressor pathway. J Exp Med. 1982 Sep 1;156(3):822–833. doi: 10.1084/jem.156.3.822. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Benacerraf B., Germain R. N. A single major pathway of T-lymphocyte interactions in antigen-specific immune suppression. Scand J Immunol. 1981;13(1):1–10. doi: 10.1111/j.1365-3083.1981.tb00104.x. [DOI] [PubMed] [Google Scholar]
  7. Bevan M. J. In a radiation chimaera, host H-2 antigens determine immune responsiveness of donor cytotoxic cells. Nature. 1977 Sep 29;269(5627):417–418. doi: 10.1038/269417a0. [DOI] [PubMed] [Google Scholar]
  8. Cantor H., Gershon R. K. Immunological circuits: cellular composition. Fed Proc. 1979 Jun;38(7):2058–2064. [PubMed] [Google Scholar]
  9. Feldmann M., Kontiainen S. Suppressor cell induction in vitro. II. Cellular requirements of suppressor cell induction. Eur J Immunol. 1976 Apr;6(4):302–305. doi: 10.1002/eji.1830060413. [DOI] [PubMed] [Google Scholar]
  10. Flood P., Yamauchi K., Singer A., Gershon R. K. Homologies between cell interaction molecular controlled by major histocompatibility complex- and Igh-V-linked genes that T cells use for communication. Tandem "adaptive" differentiation of producer and acceptor cells. J Exp Med. 1982 Nov 1;156(5):1390–1397. doi: 10.1084/jem.156.5.1390. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gershon R. K., Eardley D. D., Durum S., Green D. R., Shen F. W., Yamauchi K., Cantor H., Murphy D. B. Contrasuppression. A novel immunoregulatory activity. J Exp Med. 1981 Jun 1;153(6):1533–1546. doi: 10.1084/jem.153.6.1533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Herzenberg L. A., Okumura K., Cantor H., Sato V. L., Shen F. W., Boyse E. A., Herzenberg L. A. T-cell regulation of antibody responses: demonstration of allotype-specific helper T cells and their specific removal by suppressor T cells. J Exp Med. 1976 Aug 1;144(2):330–344. doi: 10.1084/jem.144.2.330. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Heuer J., Brüner K., Opalka B., Kölsch E. A cloned T-cell line from a tolerant mouse represents a novel antigen-specific suppressor cell type. Nature. 1982 Apr 1;296(5856):456–459. doi: 10.1038/296456a0. [DOI] [PubMed] [Google Scholar]
  14. Hodes R. J., Singer A. Cellular and genetic control of antibody responses in vitro. I. Cellular requirements for the generation of genetically controlled primary IgM responses to soluble antigens. Eur J Immunol. 1977 Dec;7(12):892–897. doi: 10.1002/eji.1830071214. [DOI] [PubMed] [Google Scholar]
  15. Kappler J. W., Marrack P. The role of H-2 linked genes in helper T-cell function. IV. Importance of T-cell genotype and host environment in I-region and Ir gene expression. J Exp Med. 1978 Dec 1;148(6):1510–1522. doi: 10.1084/jem.148.6.1510. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Katz D. H. The role of the histocompatibilty gene complex in lymphocyte defferetiation. Cold Spring Harb Symp Quant Biol. 1977;41(Pt 2):611–624. doi: 10.1101/sqb.1977.041.01.070. [DOI] [PubMed] [Google Scholar]
  17. Kontiainen S., Feldmann M. Suppressor-cell induction in vitro. IV. Target of antigen-specific suppressor factor and its genetic relationships. J Exp Med. 1978 Jan 1;147(1):110–122. doi: 10.1084/jem.147.1.110. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Ly I. A., Mishell R. I. Separation of mouse spleen cells by passage through columns of sephadex G-10. J Immunol Methods. 1974 Aug;5(3):239–247. doi: 10.1016/0022-1759(74)90108-2. [DOI] [PubMed] [Google Scholar]
  19. McDougal J. S., Shen F. W., Cort S. P., Bard J. Feedback suppression: phenotypes of T cell subsets involved in the Ly1 T cell-induced immunoregulatory circuit. J Immunol. 1980 Sep;125(3):1157–1160. [PubMed] [Google Scholar]
  20. Minami M., Furusawa S., Dorf M. E. I-J restrictions on the activation and interaction of parental and F1-derived TS3 suppressor cells. J Exp Med. 1982 Aug 1;156(2):465–479. doi: 10.1084/jem.156.2.465. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Oi V. T., Jones P. P., Goding J. W., Herzenberg L. A., Herzenberg L. A. Properties of monoclonal antibodies to mouse Ig allotypes, H-2, and Ia antigens. Curr Top Microbiol Immunol. 1978;81:115–120. doi: 10.1007/978-3-642-67448-8_18. [DOI] [PubMed] [Google Scholar]
  22. Pierres M., Germain R. N. Antigen-specific T cell-mediated suppression. IV. Role of macrophages in generation of L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT)-specific suppressor T cells in responder mouse strains. J Immunol. 1978 Oct;121(4):1306–1314. [PubMed] [Google Scholar]
  23. Rich S. S., Rich R. R. Regulatory mechanisms in cell-mediated immune responses. III. I-region control of suppressor cell interaction with responder cells in mixed lymphocyte reactions. J Exp Med. 1976 Mar 1;143(3):672–677. doi: 10.1084/jem.143.3.672. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Schwartz M., Waltenbaugh C., Dorf M., Cesla R., Sela M., Benacerraf B. Determinants of antigenic molecules responsible for genetically controlled regulation of immune responses. Proc Natl Acad Sci U S A. 1976 Aug;73(8):2862–2866. doi: 10.1073/pnas.73.8.2862. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Singer A., Hathcock K. S., Hodes R. J. Cellular and genetic control of antibody responses. V. Helper T-cell recognition of H-2 determinants on accessory cells but not B cells. J Exp Med. 1979 May 1;149(5):1208–1226. doi: 10.1084/jem.149.5.1208. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Singer A., Morrissey P. J., Hathcock K. S., Ahmed A., Scher I., Hodes R. J. Role of the major histocompatibility complex in T cell activation of B cell subpopulations Lyb-5+ and Lyb-5- B cell subpopulations differ in their requirement for major histocompatibility complex-restricted T cell recognition. J Exp Med. 1981 Aug 1;154(2):501–516. doi: 10.1084/jem.154.2.501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Sorensen C. M., Pierce C. W. Haplotype-specific suppression of antibody responses in vitro. I. Generation of genetically restricted suppressor T cells by neonatal treatment with semiallogeneic spleen cells. J Exp Med. 1981 Jul 1;154(1):35–47. doi: 10.1084/jem.154.1.35. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Sprent J. Restricted helper function of F1 leads to parent bone marrow chimeras controlled by K-end of H-2 complex. J Exp Med. 1978 Jun 1;147(6):1838–1842. doi: 10.1084/jem.147.6.1838. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Tada T., Okumura K. The role of antigen-specific T cell factors in the immune response. Adv Immunol. 1979;28:1–87. doi: 10.1016/s0065-2776(08)60799-3. [DOI] [PubMed] [Google Scholar]
  30. Tada T., Taniguchi M., David C. S. Properties of the antigen-specific suppressive T-cell factor in the regulation of antibody response of the mouse. IV. Special subregion assignment of the gene(s) that codes for the suppressive T-cell factor in the H-2 histocompatibility complex. J Exp Med. 1976 Sep 1;144(3):713–725. doi: 10.1084/jem.144.3.713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Takaoki M., Sy M. S., Tominaga A., Lowy A., Tsurufuji M., Finberg R., Benacerraf B., Greene M. I. I-J-restricted interactions in the generation of azobenzenearsonate-specific suppressor T cells. J Exp Med. 1982 Nov 1;156(5):1325–1334. doi: 10.1084/jem.156.5.1325. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Zinkernagel R. M., Callahan G. N., Althage A., Cooper S., Klein P. A., Klein J. On the thymus in the differentiation of "H-2 self-recognition" by T cells: evidence for dual recognition? J Exp Med. 1978 Mar 1;147(3):882–896. doi: 10.1084/jem.147.3.882. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. von Boehmer H., Hudson L., Sprent J. Collaboration of histoincompatible T and B lymphocytes using cells from tetraparental bone marrow chimeras. J Exp Med. 1975 Oct 1;142(4):989–997. doi: 10.1084/jem.142.4.989. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES