SummaryDendritic cells (DC), the most efficient antigen-presenting cells, are well equipped for activation of naive CD4 + T cells by their expression of high levels of major histocompatibility complex and costimulator molecules. We now demonstrate that some DC are equally well equipped for killing these same T cells. Murine splenic DC consist of both conventional CDSot-DC and a major population of CD8cx + DC. Whereas CDS-DC induce a vigorous proliferative response in CD4 T cells, CD8 + DC induce a lesser response that is associated with marked T cell apoptosis. By using various mixtures of T cells and DC from Fas-mutant Ipr/Ipr mice and Fas-ligand (FasL) mutant gld/gld mice, we show this death is due to interaction of Fas on activated T cells with FasL on CD8 + DC. Furthermore, we show by direct surface staining that CD8 + DC, but not CD8-DC, express FasL at high levels. These findings indicate that FasL + CD8 + DC are a specialized subgroup of DC with a role in the regulation of the response of primary peripheral T cells.

The MHC class II gene Aa was disrupted by targeted mutation In embryonic stem (ES) cells derived from C57BL/6 mice to prevent expression of MHC class II molecules. Contrary to previous reports, the effect of the null-mutation on T cell development was Investigated In C57BL/6 mice, which provide a defined genetic background. The complete lack of cell surface expression of MHC class II molecules In B6-Aa°IAa° homozygous mutant mice was directly demonstrated by cytofluorometrlc analysis using antl-A b and anti-la specific mAbs. Development of CD4 + CD8" T cells In the thymus was largely absent except for a small population of thymocytes expressing high levels of CD4 together with low amounts of CDS. The majority of these cells express the TCR at high density. Although mature CD4+CD8~ T cells were undetectable In the thymus, some T cells with a CD4 + CD8~TCR hlBh phenotype were found In lymph nodes and spleen. Peripheral T cells from the mutant mice can be polyclonally activated In vitro with the mltogen concanavalln A. However, they could not be stimulated with staphylococcal enterotoxln B In autologous lymphocyte reactions, thereby demonstrating the absence of MHC class II expression in these mice. Peripheral B cells In B6-A8°/Aa° mutants were functional and responded to the T cell independent antigen levan by the production of antigenspecific IgM antibodies similar to wild-type cells. The B6-Aa°IAa° mutant mice described In this study represent an important tool to Investigate the Involvement of MHC class II molecules in lymphocyte maturation and the Immune response.

The early thymus precursor population of adult mice has the capacity to generate T cells, B cells and dendritic cells (DC). These precursors were injected into the thymus of irradiated recipients in order to follow the kinetics of thymic DC development. The resultant cohort of T-lineage cells developing in the thymus was accompanied by a parallel cohort of DC, present at 10(3)-fold lower frequency. The intrathymic lifespan of these DC was as short as that of T-lineage thymocytes. As the thymic DC matured, some markers characteristic of the original precursor population gradually declined (Ly-5, c-kit, Sca-2) whereas markers characteristic of thymic DC appeared and were maintained (major histocompatibility complex class II, CD11c, NLDC-145 and CD8 alpha). Some thymic DC expressed the early B-cell marker BP-1, and BP-1 mRNA, throughout their maturation. The surface markers on thymic DC could be divided into two groups. Some markers, including class I and class II MHC, CD8 alpha and BP-1, appeared to be integral components of the DC surface. In contrast, other markers, including Thy-1, CD4 and CD8 beta, had probably been picked up from associated thymocytes.