Mechanisms of peripheral immune tolerance: conversion of the immune to the unresponsive phenotype.

Our studies on the immune response to foreign antigens are reviewed as they relate to the mechanisms of peripheral immune tolerance. The activation of suppressor T cells by distinct modes of antigen presentation is discussed. Through the use of mice expressing transgenic T-cell receptors specific for foreign antigens, we have concluded that the separable mechanisms of anergy and active suppression by CD25+ T cells work in concert to produce peripheral tolerance. In T-cell receptor Vbeta8.1 transgenic mice rendered tolerant of Mls-1a, the absence of the cell surface marker 6C10 defines the anergic population of CD4+ T cells, while 6C10+ CD4+ T cells are actively suppressed by CD25+ T cells. Through discussion of these observations, we have developed a historical perspective on recent advances in the understanding of mechanisms of peripheral tolerance.