T-cell tolerance by clonal anergy in transgenic mice with nonlymphoid expression of MHC class II I-E.
T-cell reactivity to the class II major histocompatibility complex I-E antigen is associated with T-cell antigen receptors containing the V beta gene segments V beta 17a and V beta 5. Mice expressing I-E with the normal tissue distribution (on B cells, macrophages, dendritic cells and thymic epithelium) induce tolerance to self I-E by clonal deletion in the thymus. By contrast, we find that transgenic INS-I-E mice that express I-E on pancreatic beta-cells, but not in the thymus or peripheral lymphoid organs, are tolerant to I-E but have not deleted V beta 5- and V beta 17a-bearing T cells. Moreover, whereas T-cell populations from nontransgenic mice proliferate in response to receptor crosslinking with V beta 5- and V beta 17a-specific antibodies, T cells from INS-I-E mice do not. Thus, our experiments provide direct evidence that T-cell tolerance by clonal paralysis does occur during normal T-cell development in vivo.[1]References
- T-cell tolerance by clonal anergy in transgenic mice with nonlymphoid expression of MHC class II I-E. Burkly, L.C., Lo, D., Kanagawa, O., Brinster, R.L., Flavell, R.A. Nature (1989) [Pubmed]
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