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. 1979 Nov 1;150(5):1229–1240. doi: 10.1084/jem.150.5.1229

Antigen- and receptor-driven regulatory mechanisms. II. Induction of suppressor T cells with idiotype-coupled syngeneic spleen cells

PMCID: PMC2185698  PMID: 91657

Abstract

Anti-p-azobenzenearsonate (ABA) antibodies, coupled covalently to normal syngeneic spleen cells and then given intravenously to normal animals, were found to be potent tolerogens for delayed-type hypersensitivity (DTH) to ABA. The ability of the antibody-coupled cells to induce tolerance was determined to be a result of the cross- reactive idiotype (CRI+) fraction of the antibodies, because anti-ABA antibodies lacking the CRI+ components when coupled to spleen cells were unable to cause any significant inhibition. Furthermore, genetic analysis revealed that the ability of CRI-coupled cells to inhibit ABA- specific DTH is linked to Igh-1 heavy chain allotype, in as much animals which possess heavy chain allotypes similar to that of A/J were sensitive to this inhibition. Adoptive transfer experiments provided evidence that CRI-coupled cells induce suppressor cells, and spleen cells or thymocytes from animals received CRI-coupled cells were able to transfer suppression to naive recipients. In addition, treatment with anti-Thy1.2 serum plus complement completely abrogated their ability to transfer suppression. Thus, this active suppression is a T- cell-dependent phenomenon. In investigating the specificity of these suppressor T cells, it was found that they functioned in an antigen- specific manner and were unable to suppress the development of DTH to an unrelated hapten 2,4-dinitro-1-fluorobenzene.

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Selected References

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  1. Bach B. A., Greene M. I., Benacerraf B., Nisonoff A. Mechanisms of regulation of cell-mediated immunity. IV. Azobenzenearsonate-specific suppressor factor(s) bear cross-reactive idiotypic determinants the expression of which is linked to the heavy-chain allotype linkage group of genes. J Exp Med. 1979 May 1;149(5):1084–1098. doi: 10.1084/jem.149.5.1084. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bach B. A., Sherman L., Benacerraf B., Greene M. I. Mechanisms of regulation of cell-mediated immunity. II. Induction and suppression of delayed-type hypersensitivity to azobenzenearsonate-coupled syngeneic cells. J Immunol. 1978 Oct;121(4):1460–1468. [PubMed] [Google Scholar]
  3. Battisto J. R., Bloom B. R. Dual immunological unresponsiveness induced by cell membrane coupled hapten or antigen. Nature. 1966 Oct 8;212(5058):156–157. doi: 10.1038/212156a0. [DOI] [PubMed] [Google Scholar]
  4. Bellgrau D., Wilson D. B. Immunological studies of T-cell receptors. I. Specifically induced resistance to graft-versus-host disease in rats mediated by host T-cell immunity to alloreactive parental T cells. J Exp Med. 1978 Jul 1;148(1):103–114. doi: 10.1084/jem.148.1.103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Benacerraf B., Germain R. N. Specific suppressor responses to antigen under I region control. Fed Proc. 1979 Jun;38(7):2053–2057. [PubMed] [Google Scholar]
  6. Binz H., Wigzell H. Induction of specific immune unresponsiveness with purified mixed leukocyte culture-activated T lymphoblasts as autoimmunogen. III. Proof for the existence of autoanti-idiotypic killer T cells and transfer of suppression to normal syngeneic recipients by T or B lymphocytes. J Exp Med. 1978 Jan 1;147(1):63–76. doi: 10.1084/jem.147.1.63. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bona C., Paul W. E. Cellular basis of regulation of expression of idiotype. I. T-suppressor cells specific for MOPC 460 idiotype regulate the expression of cells secreting anti-TNP antibodies bearing 460 idiotype. J Exp Med. 1979 Mar 1;149(3):592–600. doi: 10.1084/jem.149.3.592. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bottomly K., Mathieson B. J., Mosier D. E. Anti-idiotype induced regulation of helper cell function for the response to phosphorylcholine in adult BALB/c mice. J Exp Med. 1978 Nov 1;148(5):1216–1227. doi: 10.1084/jem.148.5.1216. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Claman H. N., Miller S. D. Requirements for induction of T cell tolerance to DNFB: efficiency of membrane-associated DNFB. J Immunol. 1976 Aug;117(2):480–485. [PubMed] [Google Scholar]
  10. Cosenza H., Augustin A., Julius M. H. Induction and characterization of "autologous" anti-isiotypic antibodies. Eur J Immunol. 1977 May;7(5):273–278. doi: 10.1002/eji.1830070506. [DOI] [PubMed] [Google Scholar]
  11. Dohi Y., Nisonoff A. Suppression of idiotype and generation of suppressor T cells with idiotype-conjugated thymocytes. J Exp Med. 1979 Oct 1;150(4):909–918. doi: 10.1084/jem.150.4.909. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Greene M. I., Bach B. A., Benacerraf B. Mechanisms of regulation of cell-mediated immunity. III. The characterization of azobenzenearsonate-specific suppressor T-cell-derived-suppressor factors. J Exp Med. 1979 May 1;149(5):1069–1083. doi: 10.1084/jem.149.5.1069. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Jerne N. K. Towards a network theory of the immune system. Ann Immunol (Paris) 1974 Jan;125C(1-2):373–389. [PubMed] [Google Scholar]
  14. Ju S., Gray A., Nisonoff A. Frequency of occurrence of idiotypes associated with anti-p-azophenylarsonate antibodies arising in mice immunologically suppressed with respect to a cross-reactive idiotype. J Exp Med. 1977 Mar 1;145(3):540–556. doi: 10.1084/jem.145.3.540. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lewis G. K., Goodman J. W. Purification of functional, determinant-specific, idiotype-bearing murine T cells. J Exp Med. 1978 Oct 1;148(4):915–924. doi: 10.1084/jem.148.4.915. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Miller S. D., Wetzig R. P., Claman H. N. The induction of cell-mediated immunity and tolerance with protein antigens coupled to syngeneic lymphoid cells. J Exp Med. 1979 Mar 1;149(3):758–773. doi: 10.1084/jem.149.3.758. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Nisonoff A., Ju S. T., Owen F. L. Studies of structure and immunosuppression of cross-reactive idiotype in strain A mice. Immunol Rev. 1977;34:89–118. doi: 10.1111/j.1600-065x.1977.tb00369.x. [DOI] [PubMed] [Google Scholar]
  18. Owen F. L., Ju S. T., Nisonoff A. Presence on idiotype-specific suppressor T cells of receptors that interact with molecules bearing the idiotype. J Exp Med. 1977 Jun 1;145(6):1559–1566. doi: 10.1084/jem.145.6.1559. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Pawlak L. L., Mushinski E. B., Nisonoff A., Potter M. Evidence for the linkage of the IGC H locus to a gene controlling the idiotypic specificity of anti-p-azophenylarsonate antibodies in strain A mice. J Exp Med. 1973 Jan 1;137(1):22–31. doi: 10.1084/jem.137.1.22. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Rowley D. A., Köhler H., Schreiber H., Kaye S. T., Lorbach I. Suppression by autogenous complementary idiotypes: the priority of the first response. J Exp Med. 1976 Oct 1;144(4):946–959. doi: 10.1084/jem.144.4.946. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Sy M. S., Bach B. A., Dohi Y., Nisonoff A., Benacerraf B., Greene M. I. Antigen- and receptor-driven regulatory mechanisms. I. Induction of suppressor T cells with anti-idiotypic antibodies. J Exp Med. 1979 Nov 1;150(5):1216–1228. doi: 10.1084/jem.150.5.1216. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Tada T., Taniguchi M., Takemori T. Properties of primed suppressor T cells and their products. Transplant Rev. 1975;26:106–129. doi: 10.1111/j.1600-065x.1975.tb00177.x. [DOI] [PubMed] [Google Scholar]
  23. Taniguchi M., Hayakawa K., Tada T. Properties of antigen-specific suppressive T cell factor in the regulation of antibody response of the mouse. II. In vitro activity and evidence for the I region gene product. J Immunol. 1976 Feb;116(2):542–548. [PubMed] [Google Scholar]
  24. Tung A. S., Ju S. T., Sato S., Nisonoff A. Production of large amounts of antibodies in individual mice. J Immunol. 1976 Mar;116(3):676–681. [PubMed] [Google Scholar]

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