Activation and tolerance in CD4(+) T cells reactive to an immunoglobulin variable region

The Journal of Experimental Medicine
Christopher M SnyderL J Wysocki

Abstract

Antibody diversity creates an immunoregulatory challenge for T cells that must cooperate with B cells, yet discriminate between self and nonself. To examine the consequences of T cell reactions to the B cell receptor (BCR), we generated a transgenic (Tg) line of mice expressing a T cell receptor (TCR) specific for a kappa variable region peptide in monoclonal antibody (mAb) 36-71. The kappa epitope was originally generated by a pair of somatic mutations that arose naturally during an immune response. By crossing this TCR Tg mouse with mice expressing the kappa chain of mAb 36-71, we found that kappa-specific T cells were centrally deleted in thymi of progeny that inherited the kappaTg. Maternally derived kappaTg antibody also induced central deletion. In marked contrast, adoptive transfer of TCR Tg T cells into kappaTg recipients resulted in T and B cell activation, lymphadenopathy, splenomegaly, and the production of IgG antichromatin antibodies by day 14. In most recipients, autoantibody levels increased with time, Tg T cells persisted for months, and a state of lupus nephritis developed. Despite this, Tg T cells appeared to be tolerant as assessed by severely diminished proliferative responses to the Vkappa peptide. These re...Continue Reading

References

Feb 1, 1990·The Journal of Experimental Medicine·S C MorrisR A Eisenberg
Oct 1, 1989·European Journal of Immunology·E K Bikoff, L A Eckhardt
Jan 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·S Weiss, B Bogen
Mar 1, 1989·Research in Immunology·P Benaroch, G Bordenave
Feb 1, 1988·Clinical Immunology and Immunopathology·C L FisherP L Cohen
Dec 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·M J ShlomchikM G Weigert
Feb 1, 1987·European Journal of Immunology·P Benaroch, G Bordenave
Aug 2, 1987·Nature·M J ShlomchikM G Weigert
Dec 1, 1983·The Journal of Experimental Medicine·E K Bikoff
Jun 1, 1995·European Journal of Immunology·S K Reitan, K Hannestad
Sep 11, 1995·Journal of Immunological Methods·T ZhumabekovD Kioussis
Nov 22, 1994·Proceedings of the National Academy of Sciences of the United States of America·H C ChangS G Nathenson
Jan 1, 1996·The Journal of Experimental Medicine·F GranucciP Ricciardi-Castagnoli
Dec 1, 1995·The Journal of Clinical Investigation·R R SinghB H Hahn
Nov 15, 1996·Science·M Tessier-Lavigne, C S Goodman
Nov 24, 1999·The EMBO Journal·T ZhumaD Kioussis
Nov 9, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·M El-AmineD W Scott
Nov 28, 2000·European Journal of Immunology·L MajlessiG Bordenave
Feb 13, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·X ZhangL J Wysocki
Jul 13, 2001·European Journal of Immunology·S K Reitan, K Hannestad
Aug 8, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·C TanchotR H Schwartz
Sep 6, 2001·European Journal of Immunology·O BengtssonJ Andersson
Apr 9, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Christopher M SnyderLawrence J Wysocki
Apr 9, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Debora R SekiguchiRobert A Eisenberg
Apr 12, 2002·Nature·Elizabeth A LeadbetterAnn Marshak-Rothstein
May 29, 2002·Proceedings of the National Academy of Sciences of the United States of America·Solveig Klaebo Reitan, Kristian Hannestad
Jun 22, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ram Raj SinghBevra H Hahn
Oct 8, 2003·The Journal of Experimental Medicine·Nevil J Singh, Ronald H Schwartz
Nov 25, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Amanda M GuthLawrence J Wysocki
Dec 13, 2003·Immunity·Gregory A VigliantiAnn Marshak-Rothstein

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Citations

May 9, 2007·The Journal of Experimental Medicine·Michael M ZanganiBjarne Bogen
Dec 8, 2009·Trends in Immunology·Trygve HolmøyBjarne Bogen
Sep 14, 2007·Scandinavian Journal of Immunology·A L K HestvikT Holmoy
Nov 13, 2009·Scandinavian Journal of Immunology·B Bogen, P Ruffini
Oct 30, 2004·Current Opinion in Immunology·Laurent K VerkoczyDavid Nemazee
Dec 20, 2012·Autoimmunity·Thiago DetanicoLawrence J Wysocki
Dec 5, 2019·Proceedings of the National Academy of Sciences of the United States of America·Peter Csaba HuszthyBjarne Bogen
Jan 22, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ryan M O'ConnellGenhong Cheng
May 31, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Thiago DetanicoLawrence J Wysocki
Aug 17, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kristin Aas-HanssenLudvig A Munthe
Jan 24, 2017·PloS One·J Benjamin St ClairLawrence J Wysocki
Aug 15, 2020·Frontiers in Immunology·Sylvain MeunierBernard Maillère
Aug 6, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ludvig André MuntheBjarne Bogen
May 31, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ryan A HeiserLawrence J Wysocki
Aug 6, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Wenzhong GuoLawrence J Wysocki

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Methods Mentioned

BETA
transgenic
PCR
FCS
FACS

Software Mentioned

CELL [UNK]
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