Tolerance in CD4+ helper T lymphocytes is an effective way of preventing immune responses to protein antigens because helper T cells are necessary inducers of both cellmediated and humoral immune responses to proteins. This realization has been the impetus for a large amount of work on the mechanisms of tolerance in CD4+ T cells. Immunologists have also developed experimental models for studying tolerance in CD4+ T cells that have proved to be quite informative. Also, many of the therapeutic strategies that are being developed to induce tolerance to transplants and autoantigens are targeted to these T cells. Therefore, much of the following discussion, especially of peripheral tolerance, focuses on CD4+ T cells. Less is known about peripheral tolerance in CD8+ T cells, and this is summarized at the end of the section.
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