T Lymphocyte Tolerance: From Thymic Deletion to Peripheral Control Mechanisms

Abstract

This chapter discusses the central and peripheral tolerance in the T-cell population and self-tolerance in the B-cell population. The understanding of tolerance induction in lymphocyte subpopulations is exponentially advanced in the generation of T- and B-cell receptor transgenic mice. Initial contradictions that seem to appear as different transgenic models are published and have given way to overall consensus; at least as far as central tolerance induction in the thymus is concerned. The first direct demonstration for the elimination of potentially autoreactive cells in the thymus came from studies of the T-cell repertoire to endogenous superantigens. T cells bearing Vβ segments that conferred binding to endogenous mouse mammary tumor viruses (Mtv) were absent from mice carrying these superantigens in their genome. One mechanism of deletion is terminal differentiation to short-lived effector cells that may die by apoptosis because of lymphokine depletion. The latter mechanism could be prominent for CD8 T cells. The activation of T cells requires at least two signals: a signal through the T-cell receptor and a second signal presumed to involve a co-stimulatory molecule(s) on an antigen-presenting cell.