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. 1988 Dec 1;168(6):2221–2229. doi: 10.1084/jem.168.6.2221

Deletion of potentially self-reactive T cell receptor specificities in L3T4-, Lyt-2- T cells of lpr mice [published erratum appears in J Exp Med 1989 Apr 1;169(4):1515-6]

PMCID: PMC2189150  PMID: 3264325

Abstract

The current study examines the possibility that the TCR repertoire of L3T4-, Lyt-2- cells in lpr/lpr mice is enriched for self-reactive specificities. T cells utilizing V beta 17a and V beta 8.1 gene products have been shown to be clonally eliminated in nonautoimmune mice expressing I-Ek and Mlsa/H-2k, respectively, because of their potential self reactivity. We quantitated these V beta specificities in lymph nodes and spleens of lpr/lpr mice. The results indicate that lpr- dependent L3T4-/Lyt-2- T cells, similar to normal peripheral T cells, have undergone a repertoire modification such that potential self- reactive V beta specificities have been eliminated. Evidence for tolerance in this population provides insight into the development of these aberrant cells, and may also have important implications for normal T cell development in the thymus.

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Selected References

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

  1. Adkins B., Mueller C., Okada C. Y., Reichert R. A., Weissman I. L., Spangrude G. J. Early events in T-cell maturation. Annu Rev Immunol. 1987;5:325–365. doi: 10.1146/annurev.iy.05.040187.001545. [DOI] [PubMed] [Google Scholar]
  2. Altman A., Theofilopoulos A. N., Weiner R., Katz D. H., Dixon F. J. Analysis of T cell function in autoimmune murine strains. Defects in production and responsiveness to interleukin 2. J Exp Med. 1981 Sep 1;154(3):791–808. doi: 10.1084/jem.154.3.791. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Andrews B. S., Eisenberg R. A., Theofilopoulos A. N., Izui S., Wilson C. B., McConahey P. J., Murphy E. D., Roths J. B., Dixon F. J. Spontaneous murine lupus-like syndromes. Clinical and immunopathological manifestations in several strains. J Exp Med. 1978 Nov 1;148(5):1198–1215. doi: 10.1084/jem.148.5.1198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Budd R. C., Schreyer M., Miescher G. C., MacDonald H. R. T cell lineages in the thymus of lpr/lpr mice. Evidence for parallel pathways of normal and abnormal T cell development. J Immunol. 1987 Oct 1;139(7):2200–2210. [PubMed] [Google Scholar]
  5. Davignon J. L., Budd R. C., Ceredig R., Piguet P. F., MacDonald H. R., Cerottini J. C., Vassalli P., Izui S. Functional analysis of T cell subsets from mice bearing the lpr gene. J Immunol. 1985 Oct;135(4):2423–2428. [PubMed] [Google Scholar]
  6. Dialynas D. P., Wilde D. B., Marrack P., Pierres A., Wall K. A., Havran W., Otten G., Loken M. R., Pierres M., Kappler J. Characterization of the murine antigenic determinant, designated L3T4a, recognized by monoclonal antibody GK1.5: expression of L3T4a by functional T cell clones appears to correlate primarily with class II MHC antigen-reactivity. Immunol Rev. 1983;74:29–56. doi: 10.1111/j.1600-065x.1983.tb01083.x. [DOI] [PubMed] [Google Scholar]
  7. Herron L. R., Coffman R. L., Kotzin B. L. Enhanced response of autoantibody-secreting B cells from young NZB/NZW mice to T-cell-derived differentiation signals. Clin Immunol Immunopathol. 1988 Feb;46(2):314–327. doi: 10.1016/0090-1229(88)90193-6. [DOI] [PubMed] [Google Scholar]
  8. Janeway C. A., Jr, Katz M. E. The immunobiology of the T cell response to Mls-locus-disparate stimulator cells. I. Unidirectionality, new strain combinations, and the role of Ia antigens. J Immunol. 1985 Apr;134(4):2057–2063. [PubMed] [Google Scholar]
  9. 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]
  10. Kappler J. W., Roehm N., Marrack P. T cell tolerance by clonal elimination in the thymus. Cell. 1987 Apr 24;49(2):273–280. doi: 10.1016/0092-8674(87)90568-x. [DOI] [PubMed] [Google Scholar]
  11. Kappler J. W., Wade T., White J., Kushnir E., Blackman M., Bill J., Roehm N., Marrack P. A T cell receptor V beta segment that imparts reactivity to a class II major histocompatibility complex product. Cell. 1987 Apr 24;49(2):263–271. doi: 10.1016/0092-8674(87)90567-8. [DOI] [PubMed] [Google Scholar]
  12. Kisielow P., Blüthmann H., Staerz U. D., Steinmetz M., von Boehmer H. Tolerance in T-cell-receptor transgenic mice involves deletion of nonmature CD4+8+ thymocytes. Nature. 1988 Jun 23;333(6175):742–746. doi: 10.1038/333742a0. [DOI] [PubMed] [Google Scholar]
  13. Kotzin B. L., Barr V. L., Palmer E. A large deletion within the T-cell receptor beta-chain gene complex in New Zealand white mice. Science. 1985 Jul 12;229(4709):167–171. doi: 10.1126/science.2990044. [DOI] [PubMed] [Google Scholar]
  14. Marrack P., Kappler J. T cells can distinguish between allogeneic major histocompatibility complex products on different cell types. Nature. 1988 Apr 28;332(6167):840–843. doi: 10.1038/332840a0. [DOI] [PubMed] [Google Scholar]
  15. Miescher G. C., Budd R. C., Lees R. K., MacDonald H. R. Abnormal expression of T cell receptor genes in Lyt-2- L3T4- lymphocytes of lpr mice: comparison with normal immature thymocytes. J Immunol. 1987 Mar 15;138(6):1959–1967. [PubMed] [Google Scholar]
  16. Morse H. C., 3rd, Davidson W. F., Yetter R. A., Murphy E. D., Roths J. B., Coffman R. L. Abnormalities induced by the mutant gene Ipr: expansion of a unique lymphocyte subset. J Immunol. 1982 Dec;129(6):2612–2615. [PubMed] [Google Scholar]
  17. Mountz J. D., Huppi K. E., Seldin M. F., Mushinski J. F., Steinberg A. D. T cell receptor gene expression in autoimmune mice. J Immunol. 1986 Aug 1;137(3):1029–1036. [PubMed] [Google Scholar]
  18. Nemazee D. A., Studer S., Steinmetz M., Dembić Z., Kiefer M. The lymphoproliferating cells of MRL-lpr/lpr mice are a polyclonal population that bear the T lymphocyte receptor for antigen. Eur J Immunol. 1985 Aug;15(8):760–764. doi: 10.1002/eji.1830150804. [DOI] [PubMed] [Google Scholar]
  19. Steinberg A. D., Roths J. B., Murphy E. D., Steinberg R. T., Raveche E. S. Effects of thymectomy or androgen administration upon the autoimmune disease of MRL/Mp-lpr/lpr mice. J Immunol. 1980 Aug;125(2):871–873. [PubMed] [Google Scholar]
  20. Theofilopoulos A. N., Balderas R. S., Shawler D. L., Lee S., Dixon F. J. Influence of thymic genotype on the systemic lupus erythematosus-like disease and T cell proliferation of MRL/Mp-lpr/lpr mice. J Exp Med. 1981 Jun 1;153(6):1405–1414. doi: 10.1084/jem.153.6.1405. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Wilson A., Ewing T., Owens T., Scollay R., Shortman K. T cell antigen receptor expression by subsets of Ly-2-L3T4- (CD8-CD4-) thymocytes. J Immunol. 1988 Mar 1;140(5):1470–1476. [PubMed] [Google Scholar]
  22. Wofsy D., Hardy R. R., Seaman W. E. The proliferating cells in autoimmune MRL/lpr mice lack L3T4, an antigen on "helper" T cells that is involved in the response to class II major histocompatibility antigens. J Immunol. 1984 Jun;132(6):2686–2689. [PubMed] [Google Scholar]
  23. Wofsy D., Murphy E. D., Roths J. B., Dauphinée M. J., Kipper S. B., Talal N. Deficient interleukin 2 activity in MRL/Mp and C57BL/6J mice bearing the lpr gene. J Exp Med. 1981 Nov 1;154(5):1671–1680. doi: 10.1084/jem.154.5.1671. [DOI] [PMC free article] [PubMed] [Google Scholar]

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