Extrathymic Acquisition of Tolerance by T Lymphocytes

There is now convincing evidence for the imposition of self-tolerance by means of the clonal deletion of self-reactive T cells operating within the thymus. Experiments with monoclonal antibodies directed to T-cell receptors (TCRs) that bind the class II major histocompatibility complex (MHC) molecule, I-E, or the products of the Mlsa allele of the minor lymphocyte-stimulating (Mls) locus, have demonstrated the existence of cells with anti-self TCR in I-E+ or Mlsa+ mice in the immature population of thymus lymphocytes but not in the mature intrathymic or peripheral T-cell pools (Kappler et al. 1987, 1988; MacDonald et al. 1988). Likewise, in transgenic mice expressing in many of their thymus cells a TCR specific for the male (H-Y) antigen in the context of the class I H-2Db MHC molecule, H-Y autospecific T cells are deleted in male, although not in female, mice (Kisielow et al. 1988). The most widely accepted model of deletion...