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Publication : Skewed abrogation of tolerance to a neo self-antigen in double-transgenic mice coexpressing the antigen with interleukin-1beta or interferon-gamma.

First Author  Zhang M Year  2001
Journal  Cell Immunol Volume  207
Issue  1 Pages  6-12
PubMed ID  11161447 Mgi Jnum  J:67786
Mgi Id  MGI:1931398 Doi  10.1006/cimm.2000.1750
Citation  Zhang M, et al. (2001) Skewed abrogation of tolerance to a neo self-antigen in double-transgenic mice coexpressing the antigen with interleukin-1beta or interferon-gamma. Cell Immunol 207(1):6-12
abstractText  Transgenic (Tg) mice expressing hen egg lysozyme (HEL) under the control of the alphaA-crystallin promoter exhibit tolerance to HEL by both their T- and B-cell compartments. Here, we show that double-Tg mice, coexpressing HEL with either interleukin-1beta or interferon (IFN)-gamma, demonstrated unresponsiveness to HEL by their T-cell compartment, but most of them developed antibodies against HEL following a challenge with the antigen. The abrogation of humoral tolerance was more pronounced in the HEL/IL-1 double-Tg mice than in the HEL/IFN-gamma mice. Unlike their controls, double-Tg mice exhibited remarkable levels of variability in their antibody levels. The skewed abrogation of tolerance in the double-Tg mice is proposed to be due to the cytokines' capacity to rescue from clonal deletion small numbers of T cells, which provide help to antibody producing B cells. This notion is supported by the finding that adoptive transfer of small numbers of Th1 or Th2 cells into HEL-Tg mice made possible antibody production similar to that seen in the double-Tg mice. Copyright 2001 Academic Press.
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