HEN EGG-WHITE LYSOZYME-SPECIFIC T-CELLS ELICITED IN HEN EGG-WHITE LYSOZYME-TRANSGENIC MICE RETAIN AN IMPRINT OF SELF-TOLERANCE

The characteristics of T cell self-tolerance were examined in hen egg- white lysozyme (HEL)-transgenic (Tg) mice that were tolerant to a dose of HEL that was immunogenic in non-Tg littermates. HEL-specific T cel ls were identified in the periphery of the Tg mice after immunization with 100-times more HEL than was required to achieve a response in nor mal littermates. The Tg T cells were functional in vivo as they were c apable of providing help to generate a HEL-specific antibody response. Selective deletion of T cells specific for the dominant T cell determ inant of the native protein was not the primary mechanism of T cell to lerance in the HEL-Tg mice because, similar to non-Tg littermates, the majority of lymph node (LN) and T cell clones from HEL-Tg mice were s pecific for the dominant T cell determinant of HEL. Rather, our findin gs support the idea that the HEL-reactive T cells were anergic in vivo , but could be partially activated with a strong stimulus to the immun e system (i.e., 20 nmol HEL and CFA). This conclusion is based on thre e observations: 1) proliferation in vitro to HEL by Tg LN T cells was subnormal (25% of control) and required 2 log more Ag to proliferate w hen compared with proliferation of LN from non-Tg littermates; 2) T ce ll clones isolated from HEL-Tg mice also proliferated poorly upon stim ulation with HEL and Con A, although lymphokine production from the sa me stimuli was similar to that obtained from non-Tg clones; 3) invaria bly, upon repeated antigenic stimulation in vitro, the Tg T cell clone s acquired full proliferative capacity to Ag and mitogens.