Peripheral T cell tolerance.
The most efficient way to ensure self-tolerance in the T-cell repertoire is by intrathymic deletion of self-reactive clones. Antigens not present intrathymically may, however, influence the peripheral T-cell pool in various ways. The may of course activate T cells, provided that these have the correct specificity and affinity and that the antigens are presented in sufficient amounts on professional antigen-presenting cells. They may be ignored by T cells if some of these conditions are not met. In some forms, the antigen may be toleragenic for mature T cells. If the antigens persist in an immunogenic form, unresponsiveness may eventually be imposed as the end result of a powerful immune response. Extrathymic self-antigenic components are generally encountered early in development, and the way in which these influence peripheral T lymphocytes has been studied by transgenic technology. They may be ignored by T cells if they are sequestered from the immune system, or if they are present in low amounts or on nonprofessional antigen-presenting cells which lack the appropriate accessory molecules or signals needed to activate the relevant T-cell subset. On the other hand, some of these self-antigens readily induce anergy in peripheral T cells, which may or may not involve downregulation of antigen receptors and coreceptors. Tolerance in the T-cell repertoire is therefore achieved not only by intrathymic deletion of self-reactive clones but also by several postthymic mechanisms.
Miller
J F
JF
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
Morahan
G
G
D000818:Animals; D002454:Cell Differentiation; D016207:Cytokines / Q000276:immunology; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007108:Immune Tolerance; D051379:Mice; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D016207:Cytokines; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II