Differential effect of CD8(+) and CD8(-) dendritic cells in the stimulation of secondary CD4(+) T cells

Dendritic cells (DC), in their role in initiation of the adaptive immune re sponse, have been extensively studied for their capacity to interact and st imulate naive T cells, Subsets of mature murine DC isolated directly from t he spleen have been shown to differ in their ability to induce proliferativ e responses in both primary CD4(+) and primary CD8(+) T cells; the myeloid- related CD8 alpha (-) DC induce a more Intense or prolonged proliferation o f naive T cells than do the lymphoid-related DC bearing CD8 alpha despite s imilar expression of MHC and cc-stimulatory molecules. Here we examine the interaction of these DC subpopulations with T cells already in the activate d or memory state which are known to have greater sensitivity to antigen st imulation and bear receptors with Increased capacity for signal transductio n. We show that influenza virus-specific CD4(+) T cell clones and splenic T cells from peptide-primed animals proliferated in response to antigen pres ented by separated splenic CD8(-) DC. In contrast, these T cells showed onl y weak, if any, proliferation in response to CD8(+) DC despite observable c luster formation in the cultures. The differential between the two DC types in inducing proliferation was even more pronounced than previously seen wi th primary T cells and did not reflect differential longevity of the DC in culture, altered response kinetics or deviation from IL-2 to IL-4 induction with CD8(+) DC, but was related to the levels of IL-2 induced. The deficie ncy in the CD8(+) DC was not overcome by using infectious virus rather than synthetic peptide as the antigen source. These results show that lymphoid- related CD8(+) splenic DC, despite their mature phenotype, fail to provide appropriate signals to secondary CD4(+) T cells to sustain their proliferat ion,