SUBCLASS OF DENDRITIC CELLS REGULATES THE RESPONSE OF NAIVE CD8 T-CELLS BY LIMITING THEIR IL-2 PRODUCTION

Previous work indicated that a subclass of mouse spleen dendritic cell s (DC), those bearing CD8 alpha, expresses the Fas ligand and restrict s peripheral CD4 T cell responses by initiating Pas-mediated apoptosis . To determine whether a similar regulation applies to CD8 T cells, th ey were purified from normal or from TCR-transgenic mice, and then cul tured with purified splenic CD8(+) DC or CD8(-) DC presenting either a lloantigens or the specific Ag for the TCR transgene. In all systems s tudied,the proliferative response of CD8 T cells was markedly less on stimulation with CD8(+) DC compared with conventional CD8(-) DC. Howev er, the basis of this restricted proliferation in response to CD8(+) D C was totally different for CD8 T cells than for CD4 T cells. The redu ced proliferation of CD8 T cells occurred later in the response than w ith CD4 T cells. In contrast with CD4 T cells, the reduced proliferati on of CD8 T cells occurred even with T cells from Fas-deficient lpr mi ce, or with DC from Fas ligand-deficient gld mice, indicating that Fas -induced apoptosis was not involved. Also, in contrast with CD4 T cell s, the reduced proliferation of CD8 T cells was completely reversed by the addition of exogenous IL-2, Furthermore, cultures of CD8 T cells with CD8(+) DC were found to be deficient in IL-2 production. Accordin gly, although CD8(+) DC are very efficient at stimulating CD8 T cells into cell division, they are deficient at stimulating endogenous cytok ine production. The implications of these different DC regulatory syst ems are discussed.