Induction and Maintenance of Anergy in Mature T Cells

Abstract

Three models have been proposed to explain the inability of T lymphocytes to respond to self-antigens (reviewed in 1): (a) self-reactive T cells are present but are prevented from functioning by suppressor T cells (suppression); (b) self-reactive T cells are present but have been functionally inactivated following interaction with host antigens (clonal anergy); and (c) self-reactive T cells are physically deleted (clonal deletion). A growing body of conclusive evidence indicates that clonal deletion is a major mechanism of tolerance induction for those antigens expressed in the thymus, the site of T cell development.2–5 It is difficult, however, to understand how this mechanism could account for tolerance to tissue-specific antigens, expressed in low amounts outside of the thymus. A potential resolution to this paradox may be found in recent studies that provide in vivo evidence for a nondeletional mechanism of clonal anergy6–8 that may operate outside of the thymus. The characteristics of the anergy observed in vivo are strikingly similar to those described for the induction of unresponsiveness in vitro for type 1 CD4+ T cell clones. Here we review our results on the induction of anergy in T cell clones and present new data on the mechanism by which it is maintained.KeywordsCell CloneAntigenic PeptideInositol PhosphateThymic Epithelial CellClonal DeletionThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.