Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1981 Sep 1;154(3):809–820. doi: 10.1084/jem.154.3.809

Mechanisms of idiotype suppression. IV. Functional neutralization in mixtures of idiotype-specific suppressor and hapten-specific suppressor T cells

PMCID: PMC2186474  PMID: 6456322

Abstract

Specific tolerance to phosphorylcholine (PC) can be induced in BALB/c mice by neonatal injection with either pneumococcal C-polysaccharide (PnC) or anti-TEPC 15 idiotype (T15Id) antibody specific for the major idiotype (Id) of anti-PC antibody. Spleen cells from these tolerant mice exhibited T cell-mediated active suppression of anti-PC response when they were co-cultured with normal spleen cells. Suppressor cells from the PnC-injected mice appeared to bear either Lyt-1 or Lyt-2 antigens, whereas suppressor cells from anti-Id-treated mice expressed Lyt-2 antigens. Analyses of the specific receptors of these suppressor T cells, based on either adherence to PC and T15-coated petri dishes or cytolysis by rabbit anti-T15Id and monoclonal IgM anti-PC antibody with complement, revealed that receptors of PnC-induced suppressor T cells recognize PC, whereas receptors of anti-Id-induced suppressor T cells react with the T15Id. The possible interaction of the two different types of suppressor T cells was examined by co-culturing normal spleen cells with mixtures of the different suppressor cell types in various cell ratios in the presence of the T-independent PC-antigen, R36a. A brief incubation of anti-Id-induced, T15Id-specific suppressor T cells with PnC-induced, hapten-specific, and T15Id-bearing suppressor T cells resulted in complete cancellation of their suppressor function. These results suggest that idiotype network regulation may also occur among suppressor T cell population.

Full Text

The Full Text of this article is available as a PDF (772.4 KB).

Selected References

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

  1. Abbas A. K., Perry L. L., Bach B. A., Greene M. I. Idiotype-specific T cell immunity. I. Generation of effector and suppressor T lymphocytes reactive with myeloma idiotypic determinants. J Immunol. 1980 Mar;124(3):1160–1166. [PubMed] [Google Scholar]
  2. Alevy Y. G., Bellone C. J. Anti-phenyltrimethylamino immunity in mice. II. L-Tyrosine-p-azophenyltrimethylammonium-induced suppressor T cells selectively inhibit the expression of B-cell clones bearing a cross-reactive idiotype. J Exp Med. 1980 Mar 1;151(3):528–541. doi: 10.1084/jem.151.3.528. [DOI] [PMC free article] [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. 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]
  5. 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]
  6. Chesebro B., Metzger H. Affinity labeling of a phosphorylcholine binding mouse myeloma protein. Biochemistry. 1972 Feb 29;11(5):766–771. doi: 10.1021/bi00755a014. [DOI] [PubMed] [Google Scholar]
  7. Claman H. N., Miller S. D., Sy M. S. Suppressor cells in tolerance to contact sensitivity active against hapten-syngeneic and hapten-allogeneic determinants. J Exp Med. 1977 Jul 1;146(1):49–58. doi: 10.1084/jem.146.1.49. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cohen A., Schlesinger M. Absorption of guinea pig serum with agar. A method for elimination of itscytotoxicity for murine thymus cells. Transplantation. 1970 Jul;10(1):130–132. doi: 10.1097/00007890-197007000-00027. [DOI] [PubMed] [Google Scholar]
  9. Cosenza H., Julius M. H., Augustin A. A. Idiotypes as variable region markers: analogies between receptors on phosphorylcholine-specific T and B lymphocytes. Immunol Rev. 1977;34:3–33. doi: 10.1111/j.1600-065x.1977.tb00366.x. [DOI] [PubMed] [Google Scholar]
  10. Cosenza H., Köhler H. Specific inhibition of plaque formation to phosphorylcholine by antibody against antibody. Science. 1972 Jun 2;176(4038):1027–1029. doi: 10.1126/science.176.4038.1027. [DOI] [PubMed] [Google Scholar]
  11. Cosenza H., Köhler H. Specific suppression of the antibody response by antibodies to receptors. Proc Natl Acad Sci U S A. 1972 Sep;69(9):2701–2705. doi: 10.1073/pnas.69.9.2701. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. DRAY S., YOUNG G. O., GERALD L. IMMUNOCHEMICAL IDENTIFICATION AND GENETICS OF RABBIT GAMMA-GLOBULIN ALLOTYPES. J Immunol. 1963 Sep;91:403–415. [PubMed] [Google Scholar]
  13. 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]
  14. Eardley D. D., Gershon R. K. Induction of specific suppressor T cells in vitro. J Immunol. 1976 Jul;117(1):313–318. [PubMed] [Google Scholar]
  15. Eichmann K. Idiotype suppression. I. Influence of the dose and of the effector functions of anti-idiotypic antibody on the production of an idiotype. Eur J Immunol. 1974 Apr;4(4):296–302. doi: 10.1002/eji.1830040413. [DOI] [PubMed] [Google Scholar]
  16. Gershon R. K. A disquisition on suppressor T cells. Transplant Rev. 1975;26:170–185. doi: 10.1111/j.1600-065x.1975.tb00179.x. [DOI] [PubMed] [Google Scholar]
  17. Hetzelberger D., Eichmann K. Idiotype suppression. III. Induction of unresponsiveness to sensitization with anti-idiotypic antibody: identification of the cell types tolerized in high zone and in low zone, suppressor cell-mediated, idiotype suppression. Eur J Immunol. 1978 Dec;8(12):839–846. doi: 10.1002/eji.1830081204. [DOI] [PubMed] [Google Scholar]
  18. Hirai Y., Nisonoff A. Selective suppression of the major idiotypic component of an antihapten response by soluble T cell-derived factors with idiotypic or anti-idiotypic receptors. J Exp Med. 1980 May 1;151(5):1213–1231. doi: 10.1084/jem.151.5.1213. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. JERNE N. K., NORDIN A. A. Plaque formation in agar by single antibody-producing cells. Science. 1963 Apr 26;140(3565):405–405. [PubMed] [Google Scholar]
  20. Jerne N. K. Towards a network theory of the immune system. Ann Immunol (Paris) 1974 Jan;125C(1-2):373–389. [PubMed] [Google Scholar]
  21. Julius M. H., Simpson E., Herzenberg L. A. A rapid method for the isolation of functional thymus-derived murine lymphocytes. Eur J Immunol. 1973 Oct;3(10):645–649. doi: 10.1002/eji.1830031011. [DOI] [PubMed] [Google Scholar]
  22. Kelsoe G., Reth M., Rajewsky K. Control idiotope expression by monoclonal anti-idiotope antibodies. Immunol Rev. 1980;52:75–88. doi: 10.1111/j.1600-065x.1980.tb00331.x. [DOI] [PubMed] [Google Scholar]
  23. Kim B. S., Benewicz B. J. The lack of compensatory increases of cells producing anti-phosphorylcholine antibodies bearing other idiotypes in TEPC-15 idiotype-suppressed inbred and outbred mice. Eur J Immunol. 1980 Mar;10(3):171–175. doi: 10.1002/eji.1830100303. [DOI] [PubMed] [Google Scholar]
  24. Kim B. S., Hopkins W. J. Tolerance rendered by neonatal treatment with anti-idiotypic antibodies: induction and maintenance in athymic mice. Cell Immunol. 1978 Feb;35(2):460–465. doi: 10.1016/0008-8749(78)90164-8. [DOI] [PubMed] [Google Scholar]
  25. Kontiainen S., Feldmann M. Suppressor cell induction in vitro. I. Kinetics of induction of antigen-specific suppressor cells. Eur J Immunol. 1976 Apr;6(4):296–301. doi: 10.1002/eji.1830060412. [DOI] [PubMed] [Google Scholar]
  26. Köhler G., Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 1975 Aug 7;256(5517):495–497. doi: 10.1038/256495a0. [DOI] [PubMed] [Google Scholar]
  27. Ledbetter J. A., Herzenberg L. A. Xenogeneic monoclonal antibodies to mouse lymphoid differentiation antigens. Immunol Rev. 1979;47:63–90. doi: 10.1111/j.1600-065x.1979.tb00289.x. [DOI] [PubMed] [Google Scholar]
  28. Mage M. G., McHugh L. L., Rothstein T. L. Mouse lymphocytes with and without surface immunoglobulin: preparative scale separation in polystyrene tissue culture dishes coated with specifically purified anti-immunoglobulin. J Immunol Methods. 1977;15(1):47–56. doi: 10.1016/0022-1759(77)90016-3. [DOI] [PubMed] [Google Scholar]
  29. Marshak-Rothstein A., Fink P., Gridley T., Raulet D. H., Bevan M. J., Gefter M. L. Properties and applications of monoclonal antibodies directed against determinants of the Thy-1 locus. J Immunol. 1979 Jun;122(6):2491–2497. [PubMed] [Google Scholar]
  30. Miller S. D., Sy M. S., Claman H. N. The induction of hapten-specific T cell tolerance using hapten-modified lymphoid membranes. II. Relative roles of suppressor T cells and clone inhibition in the tolerant state. Eur J Immunol. 1977 Mar;7(3):165–170. doi: 10.1002/eji.1830070310. [DOI] [PubMed] [Google Scholar]
  31. Mishell R. I., Dutton R. W. Immunization of normal mouse spleen cell suspensions in vitro. Science. 1966 Aug 26;153(3739):1004–1006. doi: 10.1126/science.153.3739.1004. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. Rittenberg M. B., Pratt K. L. Antitrinitrophenyl (TNP) plaque assay. Primary response of Balb/c mice to soluble and particulate immunogen. Proc Soc Exp Biol Med. 1969 Nov;132(2):575–581. doi: 10.3181/00379727-132-34264. [DOI] [PubMed] [Google Scholar]
  34. SMITH R. T., BRIDGES R. A. Immunological unresponsiveness in rabbits produced by neonatal injection of defined antigens. J Exp Med. 1958 Aug 1;108(2):227–250. doi: 10.1084/jem.108.2.227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Scott D. W., Long C. A. Role of self-carriers in the immune response and tolerance. I. B-cell unresponsiveness and cytotoxic T-cell immunity induced by haptenated syngeneic lymphoid cells. J Exp Med. 1976 Nov 2;144(5):1369–1374. doi: 10.1084/jem.144.5.1369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Sharon R., McMaster P. R., Kask A. M., Owens J. D., Paul W. E. DNP-Lys-ficoll: a T-independent antigen which elicits both IgM and IgG anti-DNP antibody-secreting cells. J Immunol. 1975 May;114(5):1585–1589. [PubMed] [Google Scholar]
  37. Sher A., Cohn M. Inheritance of an idiotype associated with the immune response of inbred mice to phosphorylcholine. Eur J Immunol. 1972 Aug;2(4):319–326. doi: 10.1002/eji.1830020405. [DOI] [PubMed] [Google Scholar]
  38. Sherr D. H., Ju S. T., Weinberger J. Z., Benacerraf B., Dorf M. E. Hapten-specific T cell responses to 4-hydroxy-3-nitrophenyl acetyl. VII. Idiotype-specific suppression of plaque-forming cell responses. J Exp Med. 1981 Mar 1;153(3):640–652. doi: 10.1084/jem.153.3.640. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Shulman M., Wilde C. D., Köhler G. A better cell line for making hybridomas secreting specific antibodies. Nature. 1978 Nov 16;276(5685):269–270. doi: 10.1038/276269a0. [DOI] [PubMed] [Google Scholar]
  40. Slack J., Der-Balian G. P., Nahm M., Davie J. M. Subclass restriction of murine antibodies. II. The IgG plaque-forming cell response to thymus-independent type 1 and type 2 antigens in normal mice and mice expressing an X-linked immunodeficiency. J Exp Med. 1980 Apr 1;151(4):853–862. doi: 10.1084/jem.151.4.853. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Strayer D. S., Lee W. M., Rowley D. A., Köhler H. Anti-receptor antibody. II. Induction of long-term unresponsiveness in neonatal mice. J Immunol. 1975 Feb;114(2 Pt 2):728–733. [PubMed] [Google Scholar]
  42. Sy M. S., Dietz M. H., Germain R. N., Benacerraf B., Greene M. I. Antigen- and receptor-driven regulatory mechanisms. IV. Idiotype-bearing I-J+ suppressor T cell factors induce second-order suppressor T cells which express anti-idiotypic receptors. J Exp Med. 1980 May 1;151(5):1183–1195. doi: 10.1084/jem.151.5.1183. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Trenkner E., Riblet R. Induction of antiphosphorylcholine antibody formation by anti-idiotypic antibodies. J Exp Med. 1975 Nov 1;142(5):1121–1132. doi: 10.1084/jem.142.5.1121. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. 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]
  45. Weinberger J. Z., Germain R. N., Benacerraf B., Dorf M. E. Hapten-specific T cell responses to 4-hydroxy-3-nitrophenyl acetyl. V. Role of idiotypes in the suppressor pathway. J Exp Med. 1980 Jul 1;152(1):161–169. doi: 10.1084/jem.152.1.161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Yamamoto H., Nonaka M., Katz D. H. Suppression of hapten-specific delayed-type hypersensitivity responses in mice by idiotype-specific suppressor T cells after administration of anti-idiotypic antibodies. J Exp Med. 1979 Oct 1;150(4):818–829. doi: 10.1084/jem.150.4.818. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES