Previous work indicated that a subclass of mouse spleen dendritic cells (DC), those bearing CD8alpha, expresses the Fas ligand and restricts peripheral CD4 T cell responses by initiating Fas-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 Ipr 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.

In this study, 2 distinct populations of mature dendritic cells (DCs) were identified in the human thymus. The major population is CD11b⁻, CD11c⁺, and CD45RO^lowand does not express myeloid-related markers. It displays all the characteristics of mature DCs with a typical dendritic morphology, high surface levels of HLA-DR, CD40, CD83, and CD86, and expression of DC–lysosome-associated membrane glycoprotein messenger RNA (mRNA). In addition, CD11b⁻ thymic DCs do not express macrophage inflammatory protein-1α (MIP-1α) mRNA, but express thymus-expressed chemokine (TECK) mRNA and are able to secrete bioactive interleukin 12 (IL-12) upon stimulation. In contrast, the minor and variable thymic DC population is CD11b⁺, CD11c^high, and CD45RO^high and comprises CD83⁺CD14⁻ mature and CD83⁻CD14⁺ immature DCs. It expresses macrophage-colony stimulating factor receptor, MIP-1α mRNA and high amounts of decysin mRNA after CD40 activation, but does not express TECK and is a weak bioactive IL-12 producer. Also identified were the IL-3Rα^high plasmacytoid cells, which are present in the thymic cortex and medulla. Upon culture with IL-3, granulocyte/macrophage–colony stimulating factor, and CD40 ligand, the plasmacytoid cells can adopt a phenotype resembling that of freshly isolated CD11b⁻ thymic DCs. However, these plasmacytoid-derived DCs fail to secrete bioactive IL-12; therefore, conclusions cannot be made about a direct relation between thymic plasmacytoid cells and CD11b⁻ DCs. Whereas CD11b⁺ thymic DCs appear to be related to tonsillar germinal-center DCs, the major CD11b⁻ IL-12–secreting human thymus DC population has similarities to mouse CD11b⁻ CD8⁺ DCs.