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

Transgenic (Tg) mice expressing hen egg lysozyme (HEL) under the control of the alphaA-crystallin promoter exhibit tolerance to HEL by both their T- a nd B-cell compartments. Here, we show that double-Tg mice, coexpressing HEL with either interleukin-l beta or interferon (IFN)-gamma, demonstrated unr esponsiveness to HEL by their T-cell compartment, but most of them develope d antibodies against HEL following a challenge with the antigen. The abroga tion of humoral tolerance was more pronounced in the HEL/IL-1 double-Tg mic e than in the HEL/IFN-gamma mice. Unlike their controls, double-Tg mice exh ibited remarkable levels of variability in their antibody levels. The skewe d abrogation of tolerance in the double-Tg mice is proposed to be due to th e cytokines' capacity to rescue from clonal deletion small numbers of T cel ls, which provide help to antibody producing B cells. This notion is suppor ted by the finding that adoptive transfer of small numbers of Th1 or Th2 ce lls into HEL-Tg mice made possible antibody production similar to that seen in the double-Tg mice. (C) 2001 Academic Press.