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 cells (DC), those bearing CD8 alpha, expresses the Fas ligand and restricts peripheral CD4 T cell responses by initiating Pas-mediated apoptosis. To determine whether a similar regulation applies to CD8 T cells, they were purified from normal or from TCR-transgenic mice, and then cultured with purified splenic CD8(+) DC or CD8(-) DC presenting either alloantigens or the specific Ag for the TCR transgene. In all systems studied,the proliferative response of CD8 T cells was markedly less on stimulation with CD8(+) DC compared with conventional CD8(-) DC. However, the basis of this restricted proliferation in response to CD8(+) DC was totally different for CD8 T cells than for CD4 T cells. The reduced proliferation of CD8 T cells occurred later in the response than with CD4 T cells. In contrast with CD4 T cells, the reduced proliferation of CD8 T cells occurred even with T cells from Fas-deficient lpr mice, or with DC from Fas ligand-deficient gld mice, indicating that Fas-induced apoptosis was not involved. Also, in contrast with CD4 T cells, 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. Accordingly, although CD8(+) DC are very efficient at stimulating CD8 T cells into cell division, they are deficient at stimulating endogenous cytokine production. The implications of these different DC regulatory systems are discussed.