Class II MHC-bearing keratinocytes induce antigen-specific unresponsiveness in hapten-specific Th1 clones.

Previous studies of Ia+ keratinocytes (KC) indicated that they functioned poorly or not at all when utilized as accessory cells for T cell activation. When Ia+ KC were modified with trinitrobenzene sulfonic acid, these cells did not induce a proliferative response in the TNP-specific, 1-Ek-restricted Th1 clone SE-4 (less than 5% of control). Analysis of supernatants generated from SE-4 cells incubated with these non-stimulatory accessory cells revealed low levels of IL-3 and IFN-gamma, but an absence of IL-2, when compared with supernatants generated from SE-4 cells stimulated with TNP-modified cultured Langerhans' cells that contain high levels of all of these lymphokines. Incubation of SE-4 cells with TNP-modified Ia+, but not Ia- KC or FITC-modified Ia+ KC, resulted in unresponsiveness to subsequent stimulation with TNP-modified functional accessory cells. Blocking studies with anti-class II MHC mAb revealed that the induction of unresponsiveness by hapten-modified Ia+ KC was restricted to the I-Ek molecule. Thus, the Ag and MHC specificities of unresponsiveness induced by TNP-modified Ia+ KC were identical to those observed for the proliferation of this clone in response to TNP-modified functional accessory cells. These data indicate the existence of a naturally occurring population of Ia+ cells that, after hapten-modification, induce an unresponsive state instead of proliferation of T cells.