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. 1979 Oct 1;150(4):909–918. doi: 10.1084/jem.150.4.909

Suppression of idiotype and generation of suppressor T cells with idiotype-conjugated thymocytes

PMCID: PMC2185667  PMID: 159936

Abstract

Inoculation of A/J mice with syngeneic thymocytes conjugated with specifically purified A/J anti-phenylarsonate (anti-Ar) antibodies, selectively suppressed the subsequent synthesis of those anti-Ar antibodies which carry the major cross-reactive idiotype. High titers of anti-Ar antibodies were produced upon subsequent immunization but in most mice the idiotype was undetectable. Suppression similarly occurred in F1(A/J X BALB/c) and in C.AL-20 mice. Although some mice were suppressed when unconjugated antibody was injected, the suppressive effect was much more pronounced, particularly in the F1 and C.AL-20 recipients, when the antibody was coupled to thymocytes. The state of suppression could be adoptively transferred with T cells to mildly irradiated syngeneic recipients. A population enriched for B cells had little if any suppressive effect. There was no requirement for antigen in the generation of suppressors. Thymocytes conjugated with antibody did not induce idiotype-specific suppression in mice that had been recently challenged with antigen. Thymocytes from BALB/c and C57BL/10 mice were effective carriers for the anti-Ar antibodies, i.e., there was no evidence for H-2 restriction. The experiments demonstrate the feasibility of suppressing idiotype production and generating idiotype- specific suppressor T cells without the use of anti-idiotypic antibody or antigen.

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Selected References

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

  1. Anderson L. C., Binz H., Wigzell H. Specific unresponsiveness to transplantation antigens induced by auto-immunisation with syngeneic, antigen-specific T lymphoblasts. Nature. 1976 Dec 23;264(5588):778–780. doi: 10.1038/264778a0. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. 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]
  4. Bangasser S. A., Kapsalis A. A., Fraker P. J., Nisonoff A. Competition for antigen by cell populations having receptors with the same specificity but of different idiotype. J Immunol. 1975 Feb;114(2 Pt 1):610–614. [PubMed] [Google Scholar]
  5. 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]
  6. 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]
  7. 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]
  8. Binz H., Wigzell H. Shared idiotypic determinants on B and T lymphocytes reactive against the same antigenic determinants. I. Demonstration of similar or identical idiotypes on IgG molecules and T-cell receptors with specificity for the same alloantigens. J Exp Med. 1975 Jul 1;142(1):197–211. doi: 10.1084/jem.142.1.197. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Bona C., Hooghe R., Cazenave P. A., Leguérn C., Paul W. E. Cellular basis of regulation of expression of idiotype. II. Immunity to anti-MOPC-460 idiotype antibodies increases the level of anti-trinitrophenyl antibodies bearing 460 idiotypes. J Exp Med. 1979 Apr 1;149(4):815–823. doi: 10.1084/jem.149.4.815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. 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]
  12. Cheung N. K., Scherr D. H., Heghinian K. M., Benacerraf B., Dorf M. E. Immune suppression in vivo with antigen-modified syngeneic cells. I. T-cell-mediated suppression to the terpolymer poly-(Glu, Lys, Phe)n. J Exp Med. 1978 Dec 1;148(6):1539–1549. doi: 10.1084/jem.148.6.1539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. 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]
  15. Eichmann K., Falk I., Rajewsky K. Recognition of idiotypes in lymphocyte interactions. II. Antigen-independent cooperation between T and B lymphocytes that possess similar and complementary idiotypes. Eur J Immunol. 1978 Dec;8(12):853–857. doi: 10.1002/eji.1830081206. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Eichmann K. Idiotype suppression. II. Amplification of a suppressor T cell with anti-idiotypic activity. Eur J Immunol. 1975 Aug;5(8):511–517. doi: 10.1002/eji.1830050802. [DOI] [PubMed] [Google Scholar]
  18. Eig B. M., Ju S. T., Nisonoff A. Complete inhibition of the expression of an idiotype by a mechanism of B-cell dominance. J Exp Med. 1977 Dec 1;146(6):1574–1584. doi: 10.1084/jem.146.6.1574. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Germain R. N., Ju S. T., Kipps T. J., Benacerraf B., Dorf M. E. Shared idiotypic determinants on antibodies and T-cell-derived suppressor factor specific for the random terpolymer L-glutamic acid60-L-alanine30-L-tyrosine10. J Exp Med. 1979 Mar 1;149(3):613–622. doi: 10.1084/jem.149.3.613. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Golub E. S. Brain-associated theta antigen: reactivity of rabbit anti-mouse brain with mouse lymphoid cells. Cell Immunol. 1971 Aug;2(4):353–361. doi: 10.1016/0008-8749(71)90070-0. [DOI] [PubMed] [Google Scholar]
  21. Greene M. I., Sugimoto M., Benacerraf B. Mechanisms of regulation of cell-mediated immune responses. I. Effect of the route of immunization with TNP-coupled syngeneic cells on the induction and suppression of contact sensitivity to picryl chloride. J Immunol. 1978 May;120(5):1604–1611. [PubMed] [Google Scholar]
  22. Hart D. A., Wang A. L., Pawlak L. L., Nisonoff A. Suppression of idiotypic specificities in adult mice by administration of antiidiotypic antibody. J Exp Med. 1972 Jun 1;135(6):1293–1300. doi: 10.1084/jem.135.6.1293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. Janeway C. A., Jr, Sakato N., Eisen H. N. Recognition of immunoglobulin idiotypes by thymus-derived lymphocytes. Proc Natl Acad Sci U S A. 1975 Jun;72(6):2357–2360. doi: 10.1073/pnas.72.6.2357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Klinman N. R., Pickard A. R., Sigal N. H., Gearhart P. J., Metcalf E. S., Pierce S. K. Assessing B cell diversification by antigen receptor and precursor cell analysis. Ann Immunol (Paris) 1976 Jun-Jul;127(3-4):489–502. [PubMed] [Google Scholar]
  26. Krammer P. H., Eichmann K. T cell receptor idiotypes are controlled by genes in the heavy chain linkage group and the major histocompatibility complex. Nature. 1977 Dec 22;270(5639):733–735. doi: 10.1038/270733a0. [DOI] [PubMed] [Google Scholar]
  27. Kuettner M. G., Wang A. L., Nisonoff A. Quantitative investigations of idiotypic antibodies. VI. Idiotypic specificity as a potential genetic marker for the variable regions of mouse immunoglobulin polypeptide chains. J Exp Med. 1972 Mar 1;135(3):579–595. doi: 10.1084/jem.135.3.579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. 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]
  29. 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]
  30. Miller S. D., Sy M. S., Claman H. N. H-2 restriction of suppressor T-cell induction by hapten-modified lymphoid cells in tolerance to 1-fluoro-2,4-dinitrobenzene contact sensitization. J Exp Med. 1977 Apr 1;145(4):1071–1076. doi: 10.1084/jem.145.4.1071. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. 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]
  32. Owen F. L., Ju S. T., Nisonoff A. Binding to idiotypic determinants of large proportions of thymus-derived lymphocytes in idiotypically suppressed mice. Proc Natl Acad Sci U S A. 1977 May;74(5):2084–2088. doi: 10.1073/pnas.74.5.2084. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. 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]
  34. Owen F. L., Nisonoff A. Effect of idiotype-specific suppressor T cells on primary and secondary responses. J Exp Med. 1978 Jul 1;148(1):182–194. doi: 10.1084/jem.148.1.182. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Ramseier H., Lindenmann J. Aliotypic antibodies. Transplant Rev. 1972;10:57–96. doi: 10.1111/j.1600-065x.1972.tb01539.x. [DOI] [PubMed] [Google Scholar]
  36. Roos D., Loos J. A. Changes in the carbohydrate metabolism of mitogenically stimulated human peripheral lymphocytes. I. Stimulation by phytohaemagglutinin. Biochim Biophys Acta. 1970 Dec 29;222(3):565–582. doi: 10.1016/0304-4165(70)90182-0. [DOI] [PubMed] [Google Scholar]
  37. 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]
  38. Strayer D. S., Cosenza H., Lee W. M., Rowley D. A., Köhler H. Neonatal tolerance induced by antibody against antigen-specific receptor. Science. 1974 Nov 15;186(4164):640–643. doi: 10.1126/science.186.4164.640. [DOI] [PubMed] [Google Scholar]
  39. 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]
  40. Ward K., Cantor H., Nisonoff A. Analysis of the cellular basis of idiotype-specific suppression. J Immunol. 1978 Jun;120(6):2016–2019. [PubMed] [Google Scholar]
  41. Woodland R., Cantor H. Idiotype-specific T helper cells are required to induce idiotype-positive B memory cells to secrete antibody. Eur J Immunol. 1978 Aug;8(8):600–606. doi: 10.1002/eji.1830080812. [DOI] [PubMed] [Google Scholar]

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