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. 1995 May 1;181(5):1875–1880. doi: 10.1084/jem.181.5.1875

Autoantibodies produced spontaneously by young 1pr mice carry transforming growth factor beta and suppress cytotoxic T lymphocyte responses

PMCID: PMC2192013  PMID: 7722461

Abstract

Young MRL/MPJ-lpr (lpr) mice 8-12 wk old challenged with alloantigen had significantly lower specific cytolytic T lymphocyte (CTL) responses than control MRL/MPJ +/+ mice. Serum from lpr mice compared with serum from ++ or normal C3H mice powerfully suppressed CTL responses in mixed lymphocyte cultures (MLC); absorbing lpr serum on protein G, adding antibody against transforming growth factor beta (TGF-beta) to cultures or dissociating immunoglobulin G (IgG) and TGF-beta before additions to cultures prevented suppression. Apparently autoantibody, similar to IgG produced by normal mice in response to immunization, carries TGF-beta which suppresses CTL responses in vivo and in vitro.

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Selected References

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  1. 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]
  2. Bertoletti A., Costanzo A., Chisari F. V., Levrero M., Artini M., Sette A., Penna A., Giuberti T., Fiaccadori F., Ferrari C. Cytotoxic T lymphocyte response to a wild type hepatitis B virus epitope in patients chronically infected by variant viruses carrying substitutions within the epitope. J Exp Med. 1994 Sep 1;180(3):933–943. doi: 10.1084/jem.180.3.933. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Eisenberg R. A., Craven S. Y., Cohen P. L. Isotype progression and clonality of anti-Sm autoantibodies in MRL/Mp-lpr/lpr mice. J Immunol. 1987 Aug 1;139(3):728–733. [PubMed] [Google Scholar]
  4. Eisenberg R. A., Tan E. M., Dixon F. J. Presence of anti-Sm reactivity in autoimmune mouse strains. J Exp Med. 1978 Feb 1;147(2):582–587. doi: 10.1084/jem.147.2.582. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Eisenberg R. A., Winfield J. B., Cohen P. L. Subclass restriction of anti-Sm antibodies in MRL mice. J Immunol. 1982 Nov;129(5):2146–2149. [PubMed] [Google Scholar]
  6. Fatenejad S., Brooks W., Schwartz A., Craft J. Pattern of anti-small nuclear ribonucleoprotein antibodies in MRL/Mp-lpr/lpr mice suggests that the intact U1 snRNP particle is their autoimmunogenic target. J Immunol. 1994 Jun 1;152(11):5523–5531. [PubMed] [Google Scholar]
  7. Jevnikar A. M., Grusby M. J., Glimcher L. H. Prevention of nephritis in major histocompatibility complex class II-deficient MRL-lpr mice. J Exp Med. 1994 Apr 1;179(4):1137–1143. doi: 10.1084/jem.179.4.1137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kim C., Siminovitch K. A., Ochi A. Reduction of lupus nephritis in MRL/lpr mice by a bacterial superantigen treatment. J Exp Med. 1991 Dec 1;174(6):1431–1437. doi: 10.1084/jem.174.6.1431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Klinman D. M., Steinberg A. D. Systemic autoimmune disease arises from polyclonal B cell activation. J Exp Med. 1987 Jun 1;165(6):1755–1760. doi: 10.1084/jem.165.6.1755. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Koup R. A. Virus escape from CTL recognition. J Exp Med. 1994 Sep 1;180(3):779–782. doi: 10.1084/jem.180.3.779. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Losman M. J., Fasy T. M., Novick K. E., Monestier M. Monoclonal autoantibodies to subnucleosomes from a MRL/Mp(-)+/+ mouse. Oligoclonality of the antibody response and recognition of a determinant composed of histones H2A, H2B, and DNA. J Immunol. 1992 Mar 1;148(5):1561–1569. [PubMed] [Google Scholar]
  12. Pisetsky D. S., McCarty G. A., Peters D. V. Mechanisms of autoantibody production in autoimmune MRL mice. J Exp Med. 1980 Nov 1;152(5):1302–1310. doi: 10.1084/jem.152.5.1302. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Rathmell J. C., Goodnow C. C. Effects of the lpr mutation on elimination and inactivation of self-reactive B cells. J Immunol. 1994 Sep 15;153(6):2831–2842. [PubMed] [Google Scholar]
  14. Rowley D. A., Stach R. M. A first or dominant immunization. I. Suppression of simultaneous cytolytic T cell responses to unrelated alloantigens. J Exp Med. 1993 Sep 1;178(3):835–840. doi: 10.1084/jem.178.3.835. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Shlomchik M. J., Madaio M. P., Ni D., Trounstein M., Huszar D. The role of B cells in lpr/lpr-induced autoimmunity. J Exp Med. 1994 Oct 1;180(4):1295–1306. doi: 10.1084/jem.180.4.1295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Stach R. M., Rowley D. A. A first or dominant immunization. II. Induced immunoglobulin carries transforming growth factor beta and suppresses cytolytic T cell responses to unrelated alloantigens. J Exp Med. 1993 Sep 1;178(3):841–852. doi: 10.1084/jem.178.3.841. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Treadwell E. L., Cohen P., Williams D., O'Brien K., Volkman A., Eisenberg R. MRL mice produce anti-Su autoantibody, a specificity associated with systemic lupus erythematosus. J Immunol. 1993 Jan 15;150(2):695–699. [PubMed] [Google Scholar]
  18. Watanabe-Fukunaga R., Brannan C. I., Copeland N. G., Jenkins N. A., Nagata S. Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis. Nature. 1992 Mar 26;356(6367):314–317. doi: 10.1038/356314a0. [DOI] [PubMed] [Google Scholar]
  19. Weidt G., Utermöhlen O., Zerrahn J., Reimann J., Deppert W., Lehmann-Grube F. CD8+ T lymphocyte-mediated antiviral immunity in mice as a result of injection of recombinant viral proteins. J Immunol. 1994 Sep 15;153(6):2554–2561. [PubMed] [Google Scholar]
  20. Wu J., Zhou T., He J., Mountz J. D. Autoimmune disease in mice due to integration of an endogenous retrovirus in an apoptosis gene. J Exp Med. 1993 Aug 1;178(2):461–468. doi: 10.1084/jem.178.2.461. [DOI] [PMC free article] [PubMed] [Google Scholar]

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