ANTIGEN PRESENTATION BY EPITHELIAL-CELLS INDUCES ANERGIC IMMUNOREGULATORY CD45RO(-CELLS AND DELETION OF CD45RA(+) T-CELLS() T)

The immunoregulatory effects of alloantigen presentation by tissue par enchymal cells to resting peripheral blood CD4(+) T cells was investig ated. Coculture of CD45RO(+) (memory) and CD45RA(+) (naive) T lymphocy tes with primary cultures of MHC class Ii-expressing epithelial cells rendered both populations of T cells hyporesponsive to a subsequent ch allenge by the same MHC molecule expressed on EBV-transformed lymphobl astoid B cell lines. However, the mechanisms responsible for the allos pecific hyporesponsiveness were distinct. For the CD45RO(+) T cells, r esponsiveness was restored by subsequent culture in the presence of IL -2; the addition of IL-2 had no effect on the reactivity of the CD45RA (+) T cells. In contrast, the naive T cells were protected from the in duction of nonresponsiveness by the presence of a neutralizing anti-CD 95 Ab during the culture with thyroid follicular cells. In addition, t he hyporesponsive CD45RO(+) T cells effected linked suppression, in th at they inhibited proliferation against a third-party DR alloantigen w hen the third-party alloantigen was coexpressed with the DR Ag against which hyporesponsiveness had been induced. These results suggest that recognition of Ag by T cells on tissue parenchymal cells plays an imp ortant role in the maintenance of peripheral T cell tolerance, inducin g nonresponsiveness in naive and memory T cells by distinct mechanisms .