Suppression turned idiotypic


Suppressive effects of lymphocytes in immune responses had first been observed in the early 1970s (see chapter 7). The phenomenon of cellular immune suppression thus preceded the network theory and research on suppressor cells was carried out initially independent of network concepts, as a paradigm in its own right. In these initial experiments suppression was mostly associated with T cells from various lymphoid organs that, admixed to antigen-stimulated lymphocyte populations, diminished their reactivity as determined by T cell proliferation assays1, 2, 3. Thus, in these initial experiments both the suppressive and the antigen-reactive lymphocytes had been T cells, so that suppression was perceived as an affair among T cells only. However, the notable exception among these early observations was a report on allotype-specific suppression of immunoglobulin production by suppressor T cells, suggesting that B cells, even without antigen-stimulation, can be a target of T cell suppression as well4. The idea that in order to produce antibodies a B lymphocyte first has to escape from the suppressive effect of suppressor T cells fascinated Jerne, who speculated that: “T cells recognizing the idiotypes of B cell receptors may be assumed likewise to maintain B cell suppression. Conversely, we could conclude that, normally, B cells remain functional because of the absence of sufficient numbers of specific suppressor T cells...”5 Jerne’s speculation provided the incentive to merge the two paradigms, suppressor T cells and idiotypic network theory.


Cell Suppression Thought Style Restriction Element Suppressor Factor Idiotypic Network 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Chapter 11 References

  1. 1.
    Droege W (1971) Amplifying and suppressive effect of thymus cells. Nature 234: 549–551PubMedCrossRefGoogle Scholar
  2. 2.
    Gershon RK, Kondo K (1971) Infectious immunological tolerance. Immunology 21: 903–914PubMedGoogle Scholar
  3. 3.
    Gershon RK, Cohen P, Hencin R, Liebhaber SA (1972) Suppressor T cells. J Immunol 108: 586–590PubMedGoogle Scholar
  4. 4.
    Herzenberg LA, Chan EL, Ravitch MM, Riblet RJ, Herzenberg LA (1973) Active suppression of immunoglobulin allotype synthesis. 3. Identification of T cells as responsible for suppression by cells from spleen, thymus, lymph node, and bone marrow. J Exp Med 137: 1311–1324PubMedCrossRefGoogle Scholar
  5. 5.
    Jerne NK (1974) Towards a network theory of the immune system. Ann Immunol (Inst Pasteur) 125C: 373Google Scholar
  6. 6.
    Raff MC (1970) Two distinct populations of peripheral lymphocytes in mice distinguishable by immunofluorescence. Immunology 19: 637–650PubMedGoogle Scholar
  7. 7.
    Cantor H, Boyse EA (1975) Functional subclasses of T lymphocytes bearing different Ly antigens. II. Cooperation between subclasses of Ly+ cells in the generation of killer activity. J Exp Med 141: 1390–1399PubMedCrossRefGoogle Scholar
  8. 8.
    Cantor H, Boyse EA (1975) Functional subclasses of T-lymphocytes bearing different Ly antigens. I. The generation of functionally distinct T-cell subclasses is a differentiative process independent of antigen. J Exp Med 141: 1376–1389PubMedCrossRefGoogle Scholar
  9. 9.
    Ledbetter JA, Herzenberg LA (1979) Xenogeneic monoclonal antibodies to mouse lymphoid differentiation antigens. Immunol Rev 47: 63–90PubMedCrossRefGoogle Scholar
  10. 10.
    Ledbetter JA, Rouse RV, Micklem HS, Herzenberg LA (1980) T cell subsets defined by expression of Lyt-1,2,3 and Thy-1 antigens. Two-parameter immunofluorescence and cytotoxicity analysis with monoclonal antibodies modifies current views. J Exp Med 152: 280–295PubMedCrossRefGoogle Scholar
  11. 11.
    Huber B, Devinsky O, Gershon RK, Cantor H (1976) Cell-mediated immunity: delayed-type hypersensitivity and cytotoxic responses are mediated by different T-cell subclasses. J Exp Med 143: 1534–1539PubMedCrossRefGoogle Scholar
  12. 12.
    Cantor H, Simpson E (1975) Regulation of the immune response by subclasses of T lymphocytes. I. Interactions between pre-killer T cells and regulatory T cells obtained from peripheral lymphoid tissues of mice. Eur J Immunol 5: 330–336PubMedCrossRefGoogle Scholar
  13. 13.
    Cantor H, Boyse EA (1975) Development and function of subclasses of T cells. J Reticuloendothel Soc 17: 115–118PubMedGoogle Scholar
  14. 14.
    Jandinski J, Cantor H, Tadakuma T, Peavy DL, Pierce CW (1976) Separation of helper T cells from suppressor T cells expressing different Ly components. I. Polyclonal activation: suppressor and helper activities are inherent properties of distinct T-cell subclasses. J Exp Med 143: 1382–1390PubMedCrossRefGoogle Scholar
  15. 15.
    Cantor H, Gershon RK (1979) Immunological circuits: cellular composition. Fed Proc 38: 2058–2064PubMedGoogle Scholar
  16. 16.
    Green DR, Flood PM, Gershon RK (1983) Immunoregulatory T-cell pathways. Annu Rev Immunol 1: 439–463PubMedCrossRefGoogle Scholar
  17. 17.
    Tada T, Taniguchi M, David CS (1976) 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 Tcell factor in the H-2 histocompatibility complex. J Exp Med 144: 713–725PubMedCrossRefGoogle Scholar
  18. 18.
    Murphy DB, Herzenberg LA, Okumura K, Herzenberg LA, McDevitt HO (1976) A new I subregion (I-J) marked by a locus (Ia-4) controlling surface determinants on suppressor T lymphocytes. J Exp Med 144: 699–712PubMedCrossRefGoogle Scholar
  19. 19.
    Tada T, Okumura K (1979) The role of antigen-specific T cell factors in the immune response. Adv Immunol 28: 1–87PubMedCrossRefGoogle Scholar
  20. 20.
    Munro AJ, Taussig MJ, Campbell R, Williams H, Lawson Y (1974) Antigen-specific T-cell factor in cell cooperation: physical properties and mapping in the left-hand (K) half of H-2. J Exp Med 140: 1579–1587PubMedCrossRefGoogle Scholar
  21. 21.
    Taussig MJ (1974) T cell factor which can replace T cells in vivo. Nature 248: 234–236PubMedCrossRefGoogle Scholar
  22. 22.
    Tada T, Okumura K, Taniguchi M (1973) Regulation of homocytotropic antibody formation in the rat. 8. An antigen-specific T cell factor that regulates anti-hapten homocytotropic antibody response. J Immunol 111: 952–961;Takemori T, Tada T (1975) Properties of antigen-specific suppressive T-cell factor in the regulation of antibody response of the mouse. I. In vivo activity and immunochemical characterization. J Exp Med 142: 1241–1253; Treves AJ, Cohen IR, Feldman M (1976) Suppressor factor secreted by T-lymphocytes from tumor-bearing mice. J Natl Cancer Inst 57: 409–414; Thomas DW, Roberts WK, Talmage DW (1975) Regulation of the immune response: production of a soluble suppressor by immune spleen cells in vitro. J Immunol 114: 1616–1622; Rich SS, Rich RR (1976) Regulatory mechanisms in cell-mediated immune responses. IV. Expression of a receptor for mixed lymphocyte reaction suppressor factor on activated T lymphocytes. J Exp Med 144: 121 4–1226; Harwell L, Marrack P, Kappler JW (1977) Suppressor T-cell inactivation of a helper T-cell factor. Nature 265: 57–59; Theze J, Kapp JA, Benacerraf B (1977) Immunosuppressive factor(s) extracted from lymphoid cells of nonresponder mice primed with L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) III Immunochemical properties of the GATspecific suppressive factor. J Exp Med 145: 839–856; Germain RN,Theze J, Waltenbaugh C, Dorf ME, Benacerraf B (1978) Antigenspecific T cell-mediated suppression. II. In vitro induction by I-J-coded L-glutamic acid50-L-tyrosine50 (GT)-specific T cell suppressor factor (GT-T8F) of suppressor T cells (T82) bearing distinct I-J determinants. J Immunol 121: 602–607; Kontiainen S, Simpson E, Bohrer E, Beverley PC, Herzenberg LA, Fitzpatrick WC, Vogt P,Torano A, McKenzie IF, Feldmann M (1978) T-cell lines producing antigen-specific suppressor factor. Nature 274: 477–480; Perry LL, Benacerraf B, Greene MI (1978) Regulation of the immune response to tumor antigen. IV. Tumor antigen-specific suppressor factor(s) bear I-J determinants and induce suppressor T cells in vivo. J Immunol 121: 2144–2147PubMedGoogle Scholar
  23. 23.
    Germain RN, Benacerraf B (1980) Helper and suppressor T cell factors. Springer Semin Immunopathol 3: 93–127PubMedCrossRefGoogle Scholar
  24. 24.
    Eichmann K, Rajewsky K (1975) Induction of T and B cell immunity by antiidiotypic antibody. Eur J Immunol 5: 661–666PubMedCrossRefGoogle Scholar
  25. 25.
    Sy MS, Bach BA, Dohi Y, Nisonoff A, Benacerraf B, Greene MI (1979) Antigen-and receptor-driven regulatory mechanisms. I. Induction of suppressor T cells with anti-idiotypic antibodies. J Exp Med 150: 1216–1228PubMedCrossRefGoogle Scholar
  26. 26.
    Sy MS, Bach BA, Brown A, Nisonoff A, Benacerraf B, Greene MI (1979) Antigen-and receptor-driven regulatory mechanisms. II. Induction of suppressor T cells with idiotype-coupled syngeneic spleen cells. J Exp Med 150: 1229-1240Google Scholar
  27. 27.
    Eichmann K (1975) Idiotype suppression. II. Amplification of a suppressor T cell with anti-idiotypic activity. Eur J Immunol 5: 511–517PubMedCrossRefGoogle Scholar
  28. 28.
    Woodland R, Cantor H (1978) Idiotype-specific T helper cells are required to induce idiotype-positive B memory cells to secrete antibody. Eur J Immunol 8: 600–606PubMedCrossRefGoogle Scholar
  29. 29.
    Hetzelberger D, Eichmann K (1978) Recognition of idiotypes in lymphocyte interactions. I. Idiotypic selectivity in the cooperation between T and B lymphocytes. Eur J Immunol 8: 846–852PubMedCrossRefGoogle Scholar
  30. 30.
    Eichmann K, Falk I, Rajewsky K (1978) Recognition of idiotypes in lymphocyte interactions. II. Antigen-independent cooperation between T and B lymphocytes that possess similar and complementary idiotypes. Eur J Immunol 8: 853–857PubMedCrossRefGoogle Scholar
  31. 31.
    Dietz MH, Sy MS, Benacerraf B, Nisonoff A, Greene MI, Germain RN (1981) Antigen-and receptor-driven regulatory mechanisms. VII. H-2-restricted antiidiotypic suppressor factor from efferent suppressor T cells. J Exp Med 153: 450–463PubMedCrossRefGoogle Scholar
  32. 32.
    Sy MS, Nisonoff A, Germain RN, Benacerraf B, Greene MI (1981) Antigenand receptor-driven regulatory mechanisms. VIII. Suppression of idiotype-negative, p-azobenzenearsonate-specific T cells results from the interaction of an anti-idiotypic second-order T suppressor cell with a cross-reactive-idiotypepositive, p-azobenzenearsonate-primed T cell target. J Exp Med 153: 1415–1425PubMedCrossRefGoogle Scholar
  33. 33.
    Takaoki M, Sy MS, Whitaker B, Nepom J, Finberg R, Germain RN, Nisonoff A, Benacerraf B, Greene MI (1982) Biologic activity of an idiotype-bearing suppressor T cell factor produced by a long-term T cell hybridoma. J Immunol 128: 49–53PubMedGoogle Scholar
  34. 34.
    Greene MI, Pierres A, Dorf ME, Benacerraf B (1977) The I-J subregion codes for determinats on suppressor factor(s) which limit the contact sensitivity response to picryl chloride. J Exp Med 146: 293–296 Greene MI, Benacerraf B (1980) Studies on hapten specific T cell immunity and suppression. Immunol Rev 50: 163–186 Minami M, Okuda K, Furusawa S, Benacerraf B, Dorf ME (1981) Analysis of T cell hybridomas. I. Characterization of H-2 and Igh-restricted monoclonal suppressor factors. J Exp Med 154: 1390–1402 Takaoki M, Sy MS, Tominaga A, Lowy A, Tsurufuji M, Finberg R, Benacerraf B, Greene MI (1982) I-J-restricted interactions in the generation of azobenzenearsonate-specific suppressor T cells. J Exp Med 156: 1325–1334 Okuda K, Minami M, Ju ST, Dorf ME (1981) Functional association of idiotypic and I-J determinants on the antigen receptor of suppressor T cells. Proc Natl Acad Sci USA 78: 4557–4561 Sherr DH, Dorf ME (1984) Characterization of anti-idiotypic suppressor T cells (Tsid) induced after antigen priming. J Immunol 133: 1142–1150PubMedCrossRefGoogle Scholar
  35. 35.
    Flood PM, Lowy A, Tominaga A, Chue B, Greene MI, Gershon RK (1983) Igh variable region-restricted T cell interactions. Genetic restriction of an antigenspecific suppressor inducer factor is imparted by an I-J+ antigen-nonspecific molecule. J Exp Med 158: 1938–1947PubMedCrossRefGoogle Scholar
  36. 36.
    Eardley DD, Shen FW, Cantor H, Gershon RK (1979) Genetic control of immunoregulatory circuits. Genes linked to the Ig locus govern communication between regulatory T-cell sets. J Exp Med 150: 44–50PubMedCrossRefGoogle Scholar
  37. 37.
    Flood PM, DeLeo AB, Old LJ, Gershon RK (1983) Relation of cell surface antigens on methylcholanthrene-induced fibrosarcomas to immunoglobulin heavy chain complex variable region-linked T cell interaction molecules. Proc Natl Acad Sci USA 80: 1683–1687PubMedCrossRefGoogle Scholar
  38. 38.
    Steinmetz M, Minard K, Horvath S, McNicholas J, Srelinger J, Wake C, Long E, Mach B, Hood L (1982) A molecular map of the immune response region from the major histocompatibility complex of the mouse. Nature 300: 35–42PubMedCrossRefGoogle Scholar
  39. 39.
    Kronenberg M, Steinmetz M, Kobori J, Kraig E, Kapp JA, Pierce CW, Sorensen CM, Suzuki G, Tada T, Hood L (1983) RNA transcripts for I-J polypeptides are apparently not encoded between the I-A and I-E subregions of the murine major histocompatibility complex. Proc Natl Acad Sci USA 80: 5704–5708PubMedCrossRefGoogle Scholar
  40. 40.
    Waltenbaugh C (1981) Regulation of immune responses by I-J gene products. I. Production and characterization of anti-I-J monoclonal antibodies. J Exp Med 154: 1570–1583PubMedCrossRefGoogle Scholar
  41. 41.
    Kanno M, Kobayashi S, Tokuhisa T, Takei I, Shinohara N, Taniguchi M (1981) Monoclonal antibodies that recognize the product controlled by a gene in the I-J subregion of the mouse H-2 complex. J Exp Med 154: 1290–1304PubMedCrossRefGoogle Scholar
  42. 42.
    Klein J, Ikezawa Z, Nagy ZA (1985) From LDH-B to J: an involuntary trip. Immunol Rev 83: 61–77 See also other articles in this issue: Dorf ME, Benacerraf B (1985) I-J as a restriction element in the suppressor T cell system. Immunol Rev 83: 23–40 Murphy DB, Horowitz MC, Homer RJ, Flood PM (1985) Genetic, serological and functional analysis of I-J molecules. Immunol Rev 83: 79–103PubMedCrossRefGoogle Scholar
  43. 43.
    Moller G (1988) Do suppressor T cells exist? Scand J Immunol 27: 247–250PubMedCrossRefGoogle Scholar
  44. 44.
    Kronenberg M, Goverman J, Haars R, Malissen M, Kraig E, Phillips L, Delovitch T, Suciu-Foca N, Hood L (1985) Rearrangement and transcription of the beta-chain genes of the T-cell antigen receptor in different types of murine lymphocytes. Nature 313: 647–653PubMedCrossRefGoogle Scholar
  45. 45.
    Eichmann K (1988) Suppression needs a new hypothesis, an answer to Göran Möller. Scand J Immunol 28: 273PubMedCrossRefGoogle Scholar
  46. 46.
    Bloom BR, Salgame P, Diamond B (1992) Revisiting and revising suppressor T cells. Immunol Today 13: 13113–13116CrossRefGoogle Scholar
  47. 47.
    Shevach EM (2000) Suppressor T cells: Rebirth, function and homeostasis. Curr Biol 10: R572–R575PubMedCrossRefGoogle Scholar
  48. 48.
    Nishizuka Y, Sakakura T (1969) Thymus and reproduction: sex-linked dysgenesia of the gonad after neonatal thymectomy in mice. Science 166: 753–755PubMedCrossRefGoogle Scholar
  49. 49.
    Sakaguchi S (2000) Regulatory T cells: key controllers of immunologic self-tolerance. Cell 101: 455–458PubMedCrossRefGoogle Scholar
  50. 50.
    Taams LS, Akbar AN, Wauben MHM (eds) (2005) Regulatory T cells in inflammation. Birkhäuser Verlag, Basel, Boston, BerlinGoogle Scholar

Further Reading

  1. Keating P, Cambrosio A (1997) Helpers and suppressors: on fictional characters in immunology. J Hist Biol 30: 381–396PubMedCrossRefGoogle Scholar
  2. Sercarz E, Oki A, Gammon G (1989) Central versus peripheral tolerance: clonal inactivation versus suppressor T cells, the second half of the ‘Thirty Years War’. Immunol Suppl 2: 9–14Google Scholar
  3. Ward K, Cantor H, Nisonoff A (1978) Analysis of the cellular basis of idiotype-specific suppression. J Immunol 120: 2016–2019PubMedGoogle Scholar
  4. Weinberger JZ, Germain RN, Benacerraf B, Dorf ME (1980) Hapten-specific T cell responses to 4-hydroxy-3-nitrophenyl acetyl. V. Role of idiotypes in the suppressor pathway. J Exp Med 152: 161–169PubMedCrossRefGoogle Scholar
  5. Benacerraf B, Germain RN (1981) A single major pathway of T-lymphocyte interactions in antigen-specific immune suppression. Scand J Immunol 13: 1–10PubMedCrossRefGoogle Scholar
  6. Dorf ME, Benacerraf B (1984) Suppressor cells and immunoregulation. Annu Rev Immunol 127–157Google Scholar
  7. Kontiainen S, Feldmann M (1979) Structural characteristics of antigen-specific suppressor factors: definition of ‘constant’ region and ‘variable’ region determinants. Thymus 1: 59–79PubMedGoogle Scholar

Copyright information

© Birkhäuser Verlag AG 2008

Personalised recommendations