Thymic Mechanisms for Inducing Tolerance to Mls
As T cells develop in the thymus, they are subjected to a number of selective events which determine the antigen recognition repertoire of mature T cells. Also, as a result of selection, T cells emerge that are able to distinguish self from non-self. A number of mechanisms have been proposed for establishing self tolerance.1 In this report, it is demonstrated that T cells developing in the thymus become tolerant of the minor lymphocyte stimulatory antigens, Mis,2-4 by at least two distinct mechanisms. Through the use of V/9-specific antibodies that identify receptors with Mls specificity,5-7 it is possible to show that tolerance to this self antigen can be acquired by clonal deletion or functional inacti-vation (clonal anergy). Whether tolerance to Mls is achieved and the type of tolerance induced appears to be critically dependent upon a number of factors, most notably the MHC haplotype, the tissue involved in antigen presentation, and the type of Mis antigen (Mls-1 or Mls-2). Here, chimeric animals are used in order to manipulate the site of tissue expression of MHC and Mls antigens. The results obtained reveal that clonal deletion is dependent on the type of MHC expressed by the bone marrow-derived elements and not on the tissue source of the Mls antigen. Furthermore, in the absence of clonal deletion, tolerance to Mls can be achieved by clonal anergy. This latter form of tolerance induction appears to be the result of interactions with radiation-resistant host elements, most likely the thymic epithelium.
KeywordsStaphylococcal Enterotoxin Clonal Deletion Bone Marrow Chimera Thymic Epithelium Clonal Anergy
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