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T-Cell Reactivity to Polymorphic MHC Determinants II. Self-reactive and Self-restricted T Cells

  • K. Heeg
  • D. Kabelitz
  • H. Wagner
  • J. Reimann
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 126)

Abstract

The clonal selection approach is simple and direct: “(1) It is necessary for survival that neither immunocytes nor antibodies should exist in the body which are reactive to more than a minimal degree with any accessible body component. (2) Since immune pattern is generated by a random process, a mechanism must exist by which any ‘self-reactive’ cells which may emerge can be eliminated or functionally inhibited. More than one mechanism may be needed to establish and maintain this intrinsic immunological tolerance toward self components” (BURNET 1972). Failure of this censorship mechanism to eliminate a “forbidden” self-reactive lymphocyte clone is autoimmune disease.

Keywords

Mixed Lymphocyte Reaction Mixed Leukocyte Reaction Tolerant Mouse Autologous Mixed Lymphocyte Reaction Receptor Phenotype 
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.

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References

  1. Altman A, Katz DH (1980) The induction of autoreactivity T lymphocytes by allogeneic effect factor (AEF): relevance to normal pathways of lymphocyte differentiation. Immunol Rev. 51: 3PubMedCrossRefGoogle Scholar
  2. Battisto JR, Ponzio NM (1981) Autologous and syngeneic mixed lymphocyte reactions and their immunological significance. Prog Allergy 28: 160PubMedGoogle Scholar
  3. Bensusson A, Meuer SC, Schlossman SF, Reinherz EL (1984) Delineation of an immunoregulatory amplifier population recognizing autologous la molecules. Analysis with human T cell clones. J Exp Med 159: 559Google Scholar
  4. Born W, Weckerle H (1982) Lympho-stromal interactions in the thymus: medullary thymocytes react with I-A determinants on autochthonous thymic stimulator cells. Eur J Immunol 12: 51PubMedCrossRefGoogle Scholar
  5. Burnet MF (1972) Auto-immunity and auto-immune disease. Medical and Technical, Lancaster, UK, p 4Google Scholar
  6. Ching LM, Marbrook J, Walker KZ (1977a) Spontaneous clones of cytotoxic T cells in culture. I. Characteristics of the response. Cell Immunol 31: 284Google Scholar
  7. Ching LM, Marbrook J, Walker KZ (1977b) Spontaneous clones of cytotoxic T cells in culture. II. Specificity of the response. Cell Immunol 31: 293Google Scholar
  8. Ching LM, Walker KZ, Marbrook J (1977c) Spontaneous clones of cytotoxic T cells in culture. III. Discriminatory lysis of pairs of syngeneic blasts induced by different mitogens. Eur J Immunol 7: 850Google Scholar
  9. Ching LM, Walker KZ, Marbrook J (1977d) Clones of cytotoxic lymphocytes in culture: The difference in specificity between stimulated and nonstimulated cytotoxic lymphocytes. Eur J Immunol 7: 846Google Scholar
  10. Claësson MH, Miller RG (1985) Functional heterogeneity in allospecific cytotoxic T lymphocyte clones. II. Development of syngeneic cytotoxicity in the absence of specific antigenic stimulation. J Immunol 134: 684Google Scholar
  11. Clayberger C, Dekruyff RH, Cantor H (1984) Immunoregulatory activities of autoreactive T-cells: An I-A-specific T cell clone mediates both help and suppression of antibody responses. J Immunol 132: 2237Google Scholar
  12. Clayberger C, Dekruyff RH, Cantor H (1985) T cell regulation of antibody responses: an I-A-specific, autoreactive T cell collaborates with antigen-specific helper T cells to promote IgG responses. 134: 691Google Scholar
  13. DosReis GA, Shevach EM (1981) The syngeneic mixed leukocyte reaction represents polyclonal activation of antigen-specific T-lymphocytes with receptors for self-la antigens. J Immunol 127: 2456Google Scholar
  14. Ellis TM, Mokanakumar T (1983) Dissociation of autologous and allogeneic mixed lymphocyte reactivity by using a monoclonal antibody specific for human T helper cells. J Immunol 131: 2323PubMedGoogle Scholar
  15. Endres RO, Marrack P, Kappler JW (1983) An IL-2-secreting T cell hybridoma that respond to a self class I histocompatibility antigen in the H-2D region. J Immunol 131: 1656PubMedGoogle Scholar
  16. Finnegan A, Needleman B, Hodes RT (1984) Activation of B-cells by autoreactive T cells: cloned autoreactive T cells activate B cells by two distinct pathways. J Immunol 133: 78PubMedGoogle Scholar
  17. Folks TM, Sell KW (1984) An autoreactive T hybridoma expressing nonspecific helper acitivity. Cell Immunol 86: 183PubMedCrossRefGoogle Scholar
  18. Gatenby PA, Kotzin BZ, Engleman EG (1981) Induction of immunoglobulin secreting cells in the human autologous mixed leukocyte reaction: regulation by helper and suppressor lymphocyte subsets defined with monoclonal antibodies. J Immunol 127: 2130PubMedGoogle Scholar
  19. Glimcher LH, Shevach EM (1982) Production of autoreactive I region restricted T cell hybridomas. J Exp Med 156: 640PubMedCrossRefGoogle Scholar
  20. Glimcher LH, Steinberg AD, House SB, Green I (1980) The autologous mixed lymphocyte reaction in strains of mice with autoimmune disease. J Immunol 125: 1832PubMedGoogle Scholar
  21. Glimcher LH, Longo DL, Green I, Schwartz RH (1981) Murine syngeneic mixed lymphocyte response. I. Target antigens are self la molecules. J Exp Med 154: 1652Google Scholar
  22. Glimcher LH, Schwartz RH, Longo DL, Singer A (1982) The specificity of the syngeneic mixed leukocyte response, a primary anti-I region T-cell proliferative response, is determined intrathymically. J Immunol 129: 987PubMedGoogle Scholar
  23. Glimcher LH, Serog B, McKean DJ, Beck BN (1985) Evidence that autoreactive T hybridomas recognize multiple epitopes on the I-Ak molecule. J Immunol 134: 1780PubMedGoogle Scholar
  24. Good MF, Boyd AW, Nossal GTV (1983) Analysis of true anti-hapten cytotoxic clones in limiting dilution microcultures after correction for “anti-self” activity: precursor frequencies, Ly-2 and Thy-1 phenotype, specificity, and statistical methods. J Immunol 130: 2046PubMedGoogle Scholar
  25. Goto M, Zwaifler NJ (1983) Characterization of the killer cell generated in the autologous mixed leukocyte reaction. J Exp Med 157: 1309PubMedCrossRefGoogle Scholar
  26. Greenberg SJ, Olanow CW, Dawson DV, Crane B, Roses AD (1984) Autologous mixed lymphocyte reaction in patients with myasthenia gravis: correlation with disease activity. J Immunol 132: 1229PubMedGoogle Scholar
  27. Hausman PB, Raff HV, Gilbert RC, Picker LJ, Stobo JD (1980) T-cells and macrophages involved in the autologous mixed lymphocyte reaction are required for the response to conventional antigen. J Immunol 125: 1374PubMedGoogle Scholar
  28. Hausman PB, Stites DB, Stobo JD (1981) Antigen-reactive T-cells can be activated by autologous macrophages in the absence of added antigen. J Exp Med 153: 476PubMedCrossRefGoogle Scholar
  29. Hausman PB, Moody ChE, Innes JB, Gibbons JJ, Wecksler ME (1983) Studies on the syngeneic mixed lymphocyte reaction. III. Development of a monoclonal antibody with high specificity for autoreactive T cells. J Exp Med 158: 1307Google Scholar
  30. Hayward AR, Mori M (1984) Human newborn autologous mixed lymphocyte response: Frequency and phenotype of responders and xenoantigen specificity. J Immunol 133: 719Google Scholar
  31. Heeg K, Wagner H (1985) Analysis of immunological tolerance to major histocompatibility complex antigens. I. High frequencies of tolerogen-specific cytotoxic T lymphocyte precursors in mice neonatally tolerized to class I major histocompatibility complex antigens. Eur J Immunol 15: 25Google Scholar
  32. Heeg K, Zielinski I, Kabelitz D, Wagner H, Reimann J (1985) Anti-MHC-reactive T-cells. II. Clonal specificity analysis of mitogen-activated murine T lymphoblasts. (submitted)Google Scholar
  33. Huber C, Merkenschlager M, Gattringer C, Royston I, Fink V, Braunsteiner H (1982) Human autologous mixed lymphocyte reactivity is primarily specific for xenoprotein determinants absorbed to antigen presenting cells during rosette formation with sheep erythrocytes. J Exp Med 155: 1222PubMedCrossRefGoogle Scholar
  34. James SP, Yenokida GG, Graeff AS, Elson CO, Strober W (1981) Immunoregulatory function of T-cells activated in the autologous mixed lymphocyte reaction. J Immunol 127: 2605PubMedGoogle Scholar
  35. Jerne NK (1984) Idiotypic networks and other preconceived ideas. Immunol Rev 79: 5PubMedCrossRefGoogle Scholar
  36. Kagan J, Choi YS (1983) Failure of the human autologous mixed lymphocyte reaction in the absence of foreign antigen. Eur J Immunol 13: 1031PubMedCrossRefGoogle Scholar
  37. Kimoto M, Yoshikubo T, Kishimoto S, Yamamura Y, Kishimoto T (1984) Polyclonal activation of xid B-cells by auto-la-reactive T cell clones. J Immunol 132: 1663PubMedGoogle Scholar
  38. Lattime EC, Golub SH, Stutman O (1980) Lyt 1 cells respond to la bearing macrophages in the mu¬rine syngeneic mixed lymphocyte reaction. Eur J Immunol 10: 723PubMedCrossRefGoogle Scholar
  39. Malkovsky M, Medawar PB, Thatcher DR, Toy J, Hunt R, Rayfield LS, Dore C (1985) Acquired immunological tolerance of foreign cells is impaired by recombinant interleukin 2 or vitamin A acetate. Proc Natl Acad Sci USA 82: 536PubMedCrossRefGoogle Scholar
  40. Miller RA, Kaplan HS (1978) Generation of cytotoxic lymphocytes in the autologous mixed lymphocyte culture. J Immunol 212: 2165Google Scholar
  41. Opelz G, Kiuchi M, Takasugi M, Terasaki PI (1975) Autologous stimulation of human lymphocyte subpopulations. J Exp Med 142: 1327PubMedCrossRefGoogle Scholar
  42. Peck AB, Wigzell H, Janeway C Jr, Andersson LC (1977) Environmental and genetic control of T cell activation in vitro: a study using isolated alloantigen-activated T-cell clones Immunol Rev 35: 146Google Scholar
  43. Pfizenmaier K, Trostmann H, Rollinghoff M, Wagner H (1975) Temporary presence of self-reactive cytotoxic T-lymphocytes during murine lymphocytic choriomeningitis. Nature 258: 238PubMedCrossRefGoogle Scholar
  44. Reimann J, Miller RG (1983a) Differentiation from precursors in athymic nude mouse bone marrow of unusual spontaneously cytolytic cells showing anti-self H-2 specificity and bearing T-cell markers. J Exp Med 158: 1672PubMedCrossRefGoogle Scholar
  45. Reimann J, Miller RG (1983b) Generation of autoreactive cytotoxic T lymphocyte under limiting dilution conditions. J Immunol 131: 2128PubMedGoogle Scholar
  46. Reimann J, Kabelitz D, Heeg K, Wagner H (1985a) Allorestricted cytotoxic T-cells. Large numbers of allo-H-2Kb-restricted anti-hapten and anti-viral cytotoxic T-cell populations clonally develop in vitro from murine splenic precursor T-cells. J Exp Med 162: 592PubMedCrossRefGoogle Scholar
  47. Rock KL, Benacerraf B (1983) MHC-restricted T cell activation: analysis with T cell hybridomas. Immunol REV 76: 29PubMedCrossRefGoogle Scholar
  48. Rock KL, Benacerraf B (1984a) Thymic T-cells are driven to expand upon interaction with self-class II major histocompatibility complex gene products on accessory cells. Proc Natl Acad Sci USA 81: 1221PubMedCrossRefGoogle Scholar
  49. Rock KL, Benacerraf B (1984b) The role of la molecules in the activation of T-lymphocytes. IV. The basis of the thymocyte IL 1 response and its possible role in the generation of the T cell repertoire. J Immunol 132: 1654PubMedGoogle Scholar
  50. Smolen JS, Luger TA, Chused TM, Steinberg AD (1981) Responder cells in the human autologous mixed lymphocyte reaction. J Clin Invest 68: 1601PubMedCrossRefGoogle Scholar
  51. Sopori ML, Cohen DA, Cherian S, Roszman TL, Kaplan AM (1984) T-lymphocytes heterogeneity in the rat: separation of distinct rat T-lymphocyte populations which respond in syngeneic and allogeneic mixed lymphocyte reactions. Cell Immunol 87: 295PubMedCrossRefGoogle Scholar
  52. Stockinger B (1984) Cytotoxic T-cell precursors revealed in neonatally tolerant mice. Proc Natl Acad Sci USA 81: 220PubMedCrossRefGoogle Scholar
  53. Stout RD (1984) Inhibition of IL 2 responsiveness of mitogen-stimulated lymphocytes by SMLR-generated plastic adherent suppressor cells. Cell Immunol 85: 168PubMedCrossRefGoogle Scholar
  54. Streilein JW (1979) Neonatal tolerance: Towards a immunogenetic definition of self. Immunol Rev 46: 125CrossRefGoogle Scholar
  55. Tomonari K (1980) Cytotoxic T cells generated in the autologous mixed lymphocyte reaction. I. Primary autologous mixed lymphocyte reaction. J Immunol 124: 1111PubMedGoogle Scholar
  56. Wecksler ME, Kozak RW (1977) Lymphocyte transformation induced by autologous cells. V. Generation of immunologic memory and specificity during the autologous mixed lymphocyte reaction. J Exp Med 146: 1833Google Scholar
  57. Wecksler ME, Moody CE, Kozak RW (1981) The autologous mixed lymphocyte reaction. Adv Immunol 31: 271CrossRefGoogle Scholar
  58. Wolos JA, Smith JB (1982) Helper cells in the autologous mixed lymphocyte reaction. III. Production of helper factor(s) distinct from interleukin 2. J Exp Med 156: 1807PubMedCrossRefGoogle Scholar
  59. Wolos JA, Smith JB (1984) Helper cells in the autologous mixed lymphocyte reaction (AMLR). IV. H-2 restriction and specificity of cytotoxic cells induced by AMLR helper factors. Cell Immunol 87: 714PubMedCrossRefGoogle Scholar
  60. Yamashita U, Shevach EM (1980) The syngeneic mixed leukocyte reaction: the genetic requirements for the recognition of self resembles the requirements for the recognition of antigen in association with self. J Immunol 124: 1773PubMedGoogle Scholar
  61. Zanetti M, Altman A, Evans K, Rogers J (1984) Autoreactive rat T-cell lines: establishment and cellular characteristics. Cell Immunol 84: 341PubMedCrossRefGoogle Scholar
  62. Zauderer M, Campbell H, Johnson DR, Seman M (1984) Helper functions of antigen-induced specific and autoreactive T-cell colonies. J Mol Cell Immunol 1: 55Google Scholar
  63. Zuberi RI, Altman A (1982) Helper factor production in murine secondary syngeneic mixed leukocyte reactions. J Immunol 128: 817PubMedGoogle Scholar
  64. Zuberi RI, Katz DH (1984) Spontaneous proliferation in unfractionated spleen cell culture: autologous mixed lymphocyte reaction ( AMLR) which can be differentially regulated by prostaglandins and lymphokines. Cell Immunol 84: 299Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1986

Authors and Affiliations

  • K. Heeg
    • 1
  • D. Kabelitz
    • 1
  • H. Wagner
    • 1
  • J. Reimann
    • 1
  1. 1.Department of Medical Microbiology and ImmunologyUniversity of UlmUlmGermany

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