Skip to main content
PMC home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1984 Apr 1;159(4):1009–1026. doi: 10.1084/jem.159.4.1009

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

PMCID: PMC2187265  PMID: 6231352

Abstract

Antiidiotypic immunity can successfully inhibit the development of antitubular basement membrane (alpha TBM) disease that produces interstitial nephritis. Rats normally immunized to produce disease, however, do not develop this regulatory and protective antiidiotypic effect. The failure to see such a regulatory response is functionally related to the influence of a nonspecific, RT7.1+, OX8-suppressor T cell that appears shortly after immunization. While this suppressor cell system can partially reduce the intensity of disease, it also limits the host's ability to specifically regulate the alpha TBM immune response and, hypothetically, leaves the disease process in an operationally active mode.

Full Text

The Full Text of this article is available as a PDF (1.4 MB).

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. Asano Y., Hodes R. J. T cell regulation of B cell activation. I-A-restricted T suppressor cells inhibit the major histocompatibility complex-restricted interactions of T helper cells with B cells and accessory cells. J Exp Med. 1983 Jun 1;157(6):1867–1884. doi: 10.1084/jem.157.6.1867. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Asano Y., Hodes R. J. T cell regulation of B cell activation: antigen-specific and antigen-nonspecific suppressor pathways are mediated by distinct T cell subpopulations. J Immunol. 1983 Mar;130(3):1061–1065. [PubMed] [Google Scholar]
  4. Askenase P. W., Hayden B. J., Gershon R. K. Augmentation of delayed-type hypersensitivity by doses of cyclophosphamide which do not affect antibody responses. J Exp Med. 1975 Mar 1;141(3):697–702. doi: 10.1084/jem.141.3.697. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Barth W. F., McLaughlin C. L., Fahey J. L. The immunoglobulins of mice. VI. Response to immunization. J Immunol. 1965 Nov;95(5):781–790. [PubMed] [Google Scholar]
  6. Benacerraf B., Germain R. N. A single major pathway of T-lymphocyte interactions in antigen-specific immune suppression. Scand J Immunol. 1981;13(1):1–10. doi: 10.1111/j.1365-3083.1981.tb00104.x. [DOI] [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. Brown C. A., Carey K., Colvin R. B. Inhibition of autoimmune tubulointerstitial nephritis in guinea pigs by heterologous antisera containing anti-idiotype antibodies. J Immunol. 1979 Nov;123(5):2102–2107. [PubMed] [Google Scholar]
  10. Cantor H., Boyse E. A. 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. 1975 Jun 1;141(6):1376–1389. doi: 10.1084/jem.141.6.1376. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Cerny J., Heusser C., Wallich R., Hammerling G. J., Eardley D. D. Immunoglobulin idiotopes expressed by T cells. I. Expression of distinct idiotopes detected by monoclonal antibodies on antigen-specific suppressor T cells. J Exp Med. 1982 Sep 1;156(3):719–730. doi: 10.1084/jem.156.3.719. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Eardley D. D., Murphy D. B., Kemp J. D., Shen F. W., Cantor H., Gershon R. K. Ly-1 inducer and Ly-1,2 acceptor T cells in the feedback suppression circuit bear an I-J-subregion controlled determinant. Immunogenetics. 1980;11(6):549–557. doi: 10.1007/BF01567824. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. 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]
  15. Gershon R. K., Kondo K. Antigenic competition between heterologous erythrocytes. I. Thymic dependency. J Immunol. 1971 Jun;106(6):1524–1531. [PubMed] [Google Scholar]
  16. 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]
  17. Kapp J. A., Pierce C. W., Theze J., Benacerraf B. Modulation of immune responses by suppressor T cells. Fed Proc. 1978 Aug;37(10):2361–2364. [PubMed] [Google Scholar]
  18. 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]
  19. Krieger A., Thoenes G. H., Günther E. Genetic control of autoimmune tubulointerstitial nephritis in rats. Clin Immunol Immunopathol. 1981 Dec;21(3):301–308. doi: 10.1016/0090-1229(81)90219-1. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Lehman D. H., Wilson C. B. Role of sensitized cells in antitubular basement membrane interstitial nephritis. Int Arch Allergy Appl Immunol. 1976;51(2):168–174. doi: 10.1159/000231589. [DOI] [PubMed] [Google Scholar]
  22. Lymphocyte differentiation antigens. Transplant Proc. 1983 Jun;15(2):1625–1639. [PubMed] [Google Scholar]
  23. Mampaso F. M., Wilson C. B. Characterization of inflammatory cells in autoimmune tubulointerstitial nephritis in rats. Kidney Int. 1983 Mar;23(3):448–457. doi: 10.1038/ki.1983.41. [DOI] [PubMed] [Google Scholar]
  24. McKearn T. J., Stuart F. P., Fitch F. W. Anti-idiotypic antibody in rat transplantation immunity. I. Production of anti-idiotypic antibody in animals repeatedly immunized with alloantigens. J Immunol. 1974 Dec;113(6):1876–1882. [PubMed] [Google Scholar]
  25. 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]
  26. 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]
  27. 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]
  28. 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]
  29. Rosenberg Y. J., Asofsky R. T cell regulation of isotype expression. The requirement for a second Ig-specific helper T cell population for the induction of IgG responses. Eur J Immunol. 1981 Sep;11(9):705–710. doi: 10.1002/eji.1830110907. [DOI] [PubMed] [Google Scholar]
  30. Röllinghoff M., Starzinski-Powitz A., Pfizenmaier K., Wagner H. Cyclophosphamide-sensitive T lymphocytes suppress the in vivo generation of antigen-specific cytotoxic T lymphocytes. J Exp Med. 1977 Feb 1;145(2):455–459. doi: 10.1084/jem.145.2.455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. 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]
  32. Weinberger J. Z., Greene M. I., Benacerraf B., Dorf M. E. Hapten-specific T-cell responses to 4-hydroxy-3-nitrophenyl acetyl. I. Genetic control of delayed-type hypersensitivity by VH and I-A-region genes. J Exp Med. 1979 Jun 1;149(6):1336–1348. doi: 10.1084/jem.149.6.1336. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. 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]
  34. Wilson C. B., Dixon F. J. Anti-glomerular basement membrane antibody-induced glomerulonephritis. Kidney Int. 1973 Feb;3(2):74–89. doi: 10.1038/ki.1973.14. [DOI] [PubMed] [Google Scholar]
  35. 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]
  36. Zanetti M., Mampaso F., Wilson C. B. Anti-idiotype as a probe in the analysis of autoimmune tubulointerstitial nephritis in the Brown Norway rat. J Immunol. 1983 Sep;131(3):1268–1273. [PubMed] [Google Scholar]
  37. Zanetti M., Wilson C. B. Characterization of anti-tubular basement membrane antibodies in rats. J Immunol. 1983 May;130(5):2173–2179. [PubMed] [Google Scholar]

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

RESOURCES