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. 1985 Dec 1;162(6):1892–1903. doi: 10.1084/jem.162.6.1892

Tolerance to parenchymal self. Regulatory role of major histocompatibility complex-restricted, OX8+ suppressor T cells specific for autologous renal tubular antigen in experimental interstitial nephritis

PMCID: PMC2187971  PMID: 2415658

Abstract

BN rats develop interstitial nephritis after immunization with rabbit, but not rat renal tubular antigen. Using RT1n rat strains that differentially express tubular antigen, we investigated the unresponsiveness of BN rats to BN tubular antigen (BN-TBM) using delayed-type hypersensitivity (DTH) responses to BN-TBM as a measure of cell-mediated immunity. Our results indicate that rat strains expressing tubular antigen respond to immunization with BN-TBM with the clonal expansion of antigen-specific, cyclophosphamide-sensitive, OX8+, MHC-restricted suppressor T cells. Such suppression appears to be relevant to the maintenance of tolerance to parenchymal self, since chronic cyclophosphamide therapy abrogates suppression and results in significant interstitial nephritis.

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Selected References

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  1. Behbehani K., Beller D. I., Unanue E. R. The effects of beryllium and other adjuvants on Ia expression by macrophages. J Immunol. 1985 Apr;134(4):2047–2049. [PubMed] [Google Scholar]
  2. Dorsch S., Roser R. Recirculating, suppressor T cells in transplantation tolerance. J Exp Med. 1977 May 1;145(5):1144–1157. doi: 10.1084/jem.145.5.1144. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Ely J. M., Greiner D. L., Lubaroff D. M., Fitch F. W. Characterization of monoclonal antibodies that define rat T cell alloantigens. J Immunol. 1983 Jun;130(6):2798–2803. [PubMed] [Google Scholar]
  4. Gorczynski R. M., MacRae S. Suppression of cytotoxic response to histoincompatible cells. II. Analysis of the role of two independent T suppressor pools in maintenance of neonatally induced allograft tolerance in mice. J Immunol. 1979 Mar;122(3):747–752. [PubMed] [Google Scholar]
  5. Groves E. S., Singer A. Role of the H-2 complex in the induction of T cell tolerance to self minor histocompatibility antigens. J Exp Med. 1983 Nov 1;158(5):1483–1497. doi: 10.1084/jem.158.5.1483. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. Kayashima K., Koga T., Onoue K. Role of T lymphocytes in adjuvant arthritis. II. Different subpopulations of T lymphocytes functioning in the development of the disease. J Immunol. 1978 Apr;120(4):1127–1131. [PubMed] [Google Scholar]
  8. Kilshaw P. J., Brent L., Pinto M. Suppressor T cells in mice made unresponsive to skin allografts. Nature. 1975 Jun 5;255(5508):489–491. doi: 10.1038/255489a0. [DOI] [PubMed] [Google Scholar]
  9. Lehman D. H., Wilson C. B., Dixon F. J. Interstitial nephritis in rats immunized with heterologous tubular basement membrane. Kidney Int. 1974 Mar;5(3):187–195. doi: 10.1038/ki.1974.23. [DOI] [PubMed] [Google Scholar]
  10. Lukic M. L., Mitchison N. A. Self- and allo-specific suppressor T cells evoked by intravenous injection of F protein. Eur J Immunol. 1984 Aug;14(8):766–768. doi: 10.1002/eji.1830140820. [DOI] [PubMed] [Google Scholar]
  11. Mann R., Zakheim B., Clayman M., McCafferty E., Michaud L., Neilson E. G. Murine interstitial nephritis. IV. Long-term cultured L3T4+ T cell lines transfer delayed expression of disease as I-A-restricted inducers of the effector T cell repertoire. J Immunol. 1985 Jul;135(1):286–293. [PubMed] [Google Scholar]
  12. Matsumoto K., McCafferty E., Neilson E. G., Gasser D. L. Mapping of the genes for tubular basement membrane antigen and a submaxillary gland protease in the rat. Immunogenetics. 1984;20(2):117–123. doi: 10.1007/BF00364483. [DOI] [PubMed] [Google Scholar]
  13. Matzinger P., Zamoyska R., Waldmann H. Self tolerance is H-2-restricted. Nature. 1984 Apr 19;308(5961):738–741. doi: 10.1038/308738a0. [DOI] [PubMed] [Google Scholar]
  14. Miller J. F., Vadas M. A., Whitelaw A., Gamble J. Role of major histocompatibility complex gene products in delayed-type hypersensitivity. Proc Natl Acad Sci U S A. 1976 Jul;73(7):2486–2490. doi: 10.1073/pnas.73.7.2486. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Muraoka S., Miller R. G. Cells in bone marrow and in T cell colonies grown from bone marrow can suppress generation of cytotoxic T lymphocytes directed against their self antigens. J Exp Med. 1980 Jul 1;152(1):54–71. doi: 10.1084/jem.152.1.54. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Neilson E. G., Gasser D. L., McCafferty E., Zakheim B., Phillips S. M. Polymorphism of genes involved in anti-tubular basement membrane disease in rats. Immunogenetics. 1983;17(1):55–65. doi: 10.1007/BF00364289. [DOI] [PubMed] [Google Scholar]
  17. Neilson E. G., McCafferty E., Mann R., Michaud L., Clayman M. Murine interstitial nephritis. III. The selection of phenotypic (Lyt and L3T4) and idiotypic (RE-Id) T cell preferences by genes in Igh-1 and H-2K characterizes the cell-mediated potential for disease expression: susceptible mice provide a unique effector T cell repertoire in response to tubular antigen. J Immunol. 1985 Apr;134(4):2375–2382. [PubMed] [Google Scholar]
  18. Neilson E. G., McCafferty E., Phillips S. M., Clayman M. D., Kelly C. J. Antiidiotypic immunity in interstitial nephritis. II. Rats developing anti-tubular basement membrane disease fail to make an antiidiotypic regulatory response: the modulatory role of an RT7.1+, OX8- suppressor T cell mechanism. J Exp Med. 1984 Apr 1;159(4):1009–1026. doi: 10.1084/jem.159.4.1009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Neilson E. G., Phillips M. Suppression of interstitial nephritis by auto-anti-idiotypic immunity. J Exp Med. 1982 Jan 1;155(1):179–189. doi: 10.1084/jem.155.1.179. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Neilson E. G., Phillips S. M. Cell-mediated immunity in interstitial nephritis. I. T lymphocyte systems in nephritic guinea pigs: the natural history and diversity of the immune response. J Immunol. 1979 Nov;123(5):2373–2380. [PubMed] [Google Scholar]
  21. Nossal G. J. Cellular mechanisms of immunologic tolerance. Annu Rev Immunol. 1983;1:33–62. doi: 10.1146/annurev.iy.01.040183.000341. [DOI] [PubMed] [Google Scholar]
  22. Nossal G. J., Pike B. L. Functional clonal deletion in immunological tolerance to major histocompatibility complex antigens. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3844–3847. doi: 10.1073/pnas.78.6.3844. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Rammensee H. G., Fink P. J., Bevan M. J. Functional clonal deletion of class I-specific cytotoxic T lymphocytes by veto cells that express antigen. J Immunol. 1984 Nov;133(5):2390–2396. [PubMed] [Google Scholar]
  24. Sakaguchi S., Fukuma K., Kuribayashi K., Masuda T. Organ-specific autoimmune diseases induced in mice by elimination of T cell subset. I. Evidence for the active participation of T cells in natural self-tolerance; deficit of a T cell subset as a possible cause of autoimmune disease. J Exp Med. 1985 Jan 1;161(1):72–87. doi: 10.1084/jem.161.1.72. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Sy M. S., Miller S. D., Claman H. N. Immune suppression with supraoptimal doses of antigen in contact sensitivity. I. Demonstration of suppressor cells and their sensitivity to cyclophosphamide. J Immunol. 1977 Jul;119(1):240–244. [PubMed] [Google Scholar]
  26. Taniguchi M., Miller J. F. Enrichment of specific suppressor T cells and characterization of their surface markers. J Exp Med. 1977 Nov 1;146(5):1450–1454. doi: 10.1084/jem.146.5.1450. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Tarcic N., Baler R., Naor D. Auto-delayed-type hypersensitivity induced in immunodeficient mice with modified self-antigens. III. Suppressive T-cell factor controls the autoreactivity against self-antigens. Scand J Immunol. 1984 Nov;20(5):389–401. doi: 10.1111/j.1365-3083.1984.tb01018.x. [DOI] [PubMed] [Google Scholar]
  28. Tarcic N., Klein B. Y., Naor D. Auto-delayed-type hypersensitivity induced in immunodeficient mice with modified self-antigens. IV. Characterization of the suppressive T-cell factor that controls the autoreactivity against self-antigens. Scand J Immunol. 1984 Nov;20(5):403–411. doi: 10.1111/j.1365-3083.1984.tb01019.x. [DOI] [PubMed] [Google Scholar]
  29. Tarcic N., Naor D. Delayed-type hypersensitivity induced in immunodeficient mice with syngeneic modified self antigens: a suggestive model of autoimmune response. Eur J Immunol. 1982 Nov;12(11):961–966. doi: 10.1002/eji.1830121112. [DOI] [PubMed] [Google Scholar]
  30. Tarcic N., Sharon R., Rosenmann E., Naor D. Auto-delayed-type hypersensitivity induced in immunodeficient mice with syngeneic modified self-antigens. II. Suppressor T cells control the autoimmune response. Scand J Immunol. 1984 Feb;19(2):111–121. doi: 10.1111/j.1365-3083.1984.tb00906.x. [DOI] [PubMed] [Google Scholar]
  31. Weigle W. O. Analysis of autoimmunity through experimental models of thyroiditis and allergic encephalomyelitis. Adv Immunol. 1980;30:159–273. doi: 10.1016/s0065-2776(08)60196-0. [DOI] [PubMed] [Google Scholar]
  32. Williams A. F., Galfrè G., Milstein C. Analysis of cell surfaces by xenogeneic myeloma-hybrid antibodies: differentiation antigens of rat lymphocytes. Cell. 1977 Nov;12(3):663–673. doi: 10.1016/0092-8674(77)90266-5. [DOI] [PubMed] [Google Scholar]
  33. Wysocki L. J., Sato V. L. "Panning" for lymphocytes: a method for cell selection. Proc Natl Acad Sci U S A. 1978 Jun;75(6):2844–2848. doi: 10.1073/pnas.75.6.2844. [DOI] [PMC free article] [PubMed] [Google Scholar]

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