Tolerance is overcome in beef insulin-transgenic mice by activation of low-affinity autoreactive T cells

European Journal of Immunology
L PoplonskiJ Wither

Abstract

To gain insight into the factors controlling the maintenance or loss of T cell self tolerance we produced beef insulin (BI)-transgenic BALB/c mice. Transgenic mice express BI under control of the human insulin promoter and secrete physiological amounts of beef insulin. Although these mice are tolerant to BI, as evidenced by the lack of insulin-specific IgG antibody production following intraperitoneal immunization, tolerance is not complete. Footpad immunization results in a weak antigen-specific T cell proliferative response, indicating the presence of self-reactive BI-specific T cell in the periphery. These T cells are functional in vivo, providing support for IgG1, IgG2a, and IgG2b BI-specific antibody production, but require higher higher concentrations of antigen than nontransgenic T cells (both in vivo and following recall responses in vitro) to become activated. In vitro, BI-specific T cell proliferation in BI-transgenic mice can be largely restored by addition of interleukin-2, indicating that a significant component of T cell tolerance is mediated by anergy. To characterize the autoreactive T cells that become activated when tolerance is broken, BI-specific T cell hybridomas were generated from transgenic mice and comp...Continue Reading

References

Jan 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·R CibottiP Kourilsky
Jan 1, 1992·Annual Review of Immunology·B R BloomP Salgame
Jan 1, 1992·Annual Review of Immunology·J F Miller, G Morahan
Jan 1, 1992·The Journal of Experimental Medicine·E E Eynon, D C Parker
Dec 21, 1990·Science·L A JonesA M Kruisbeek
Apr 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·P J WhiteleyJ A Kapp
Oct 22, 1987·The New England Journal of Medicine·R F SeldenH M Goodman
Apr 24, 1987·Cell·J W KapplerP Marrack
Apr 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·D BucchiniJ Jami
May 4, 1986·Nature·R F SeldenH M Goodman
Aug 1, 1983·The Journal of Experimental Medicine·R ShimonkevitzH Grey
Mar 6, 1980·Nature·G I BellH M Goodman
Nov 1, 1993·The Journal of Experimental Medicine·C G Romball, W O Weigle

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Citations

Feb 6, 2002·Springer Seminars in Immunopathology·A Iglesias
Mar 6, 2004·Seminars in Cancer Biology·Tony Talebi, Jeffrey S Weber
Aug 30, 2001·Nature Immunology·E Gilboa
Feb 21, 2002·The Journal of Experimental Medicine·Linh T NguyenPamela S Ohashi
Dec 2, 2005·Current Opinion in Hematology·John Barrett, Katayoun Rezvani
Apr 27, 2000·American Journal of Respiratory Cell and Molecular Biology·S M DubinettS Sharma
Oct 8, 1999·Immunity·E Gilboa
Oct 25, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·M P RileyA J Caton
Sep 21, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·K E de VisserA M Kruisbeek
Jul 22, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Zsolt IllésVijay K Kuchroo
Mar 20, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·F De BenedettiA Martini
Jan 5, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tanina A CordaroAda M Kruisbeek
Dec 22, 1999·The Journal of Immunology : Official Journal of the American Association of Immunologists·C T NugentL A Sherman
Sep 7, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·P MukherjeeS J Gendler

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