Clonal Anergy in Transgenic Mice with Pancreatic Expression of MHC Class II I-E
Experimental conditions whereby T cell tolerance can be established and maintained have been investigated and defined in many systems. However, the mechanisms of tolerance in these systems and their relevance to tolerance induction during normal T cell development in vivo is still not fully understood. The development of monoclonal antibodies (mAbs) to T cell receptor (TcR) vβ chains, and the observation that certain Vβ chains are associated with reactivity to antigens such as I-E (Kappler, et al. 1987b) and Mls (Kappler, et al. 1988; MacDonald, et al. 1988) has provided in vivo evidence for clonal deletion. Thus, Kappler et al. showed that T cells utilizing the Vβl7a TcR gene which is identified by mAb KJ23 are generally reactive to I-E and are present in I-E negative mice but deleted in the thymus of I-E expressing mouse strains (Kappler, et al. 1987ab, Marrack, et al. 1988). The ability to monitor the presence or absence of antigen-reactive T cells offers a valuable alternative to functional measurements and provides a means to determine mechanisms of T cell tolerance. There is now in vitro evidence for clonal paralysis of T cells. T cell clones are reportedly inactivated upon exposure to antigen in the presence of human T cell clones (Lamb, et al. 1983), chemically modified spleen cells (Jenkins and Schwartz, 1987), purified MHC class II on planar membranes (Quill and Schwartz, 1987), class II+ keratinocytes (Gaspari, et al. 1988), and I-E+ islet cells (Markmann, et al. 1988).
KeywordsStimulation Index Cell Tolerance Clonal Deletion Howard Hughes Medical Institute Clonal Anergy
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