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  • Title: Hen egg-white lysozyme-specific T cells elicited in hen egg-white lysozyme-transgenic mice retain an imprint of self-tolerance.
    Author: Yule TD, Basten A, Allen PM.
    Journal: J Immunol; 1993 Sep 15; 151(6):3057-69. PubMed ID: 8376768.
    Abstract:
    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 cells were identified in the periphery of the Tg mice after immunization with 100-times more HEL than was required to achieve a response in normal littermates. The Tg T cells were functional in vivo as they were capable of providing help to generate a HEL-specific antibody response. Selective deletion of T cells specific for the dominant T cell determinant of the native protein was not the primary mechanism of T cell tolerance 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 specific for the dominant T cell determinant of HEL. Rather, our findings support the idea that the HEL-reactive T cells were anergic in vivo, but could be partially activated with a strong stimulus to the immune system (i.e., 20 nmol HEL and CFA). This conclusion is based on three 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 when compared with proliferation of LN from non-Tg littermates; 2) T cell clones isolated from HEL-Tg mice also proliferated poorly upon stimulation with HEL and Con A, although lymphokine production from the same stimuli was similar to that obtained from non-Tg clones; 3) invariably, upon repeated antigenic stimulation in vitro, the Tg T cell clones acquired full proliferative capacity to Ag and mitogens.
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