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 response, have been extensively studied for their capacity to interact and stimulate naive T cells. Subsets of mature murine DC isolated directly from the spleen have been shown to differ in their ability to induce proliferative responses in both primary CD4(+) and primary CD8(+) T cells; the myeloid-related CD8alpha(-) DC induce a more intense or prolonged proliferation of naive T cells than do the lymphoid-related DC bearing CD8alpha despite similar expression of MHC and co-stimulatory molecules. Here we examine the interaction of these DC subpopulations with T cells already in the activated or memory state which are known to have greater sensitivity to antigen stimulation and bear receptors with increased capacity for signal transduction.

Regulation of T cell cytokine production by dendritic cells.

Previous work has established that the dendritic cells (DC) of mouse spleen regulate the IL-2 production, and hence the extent of proliferation, of the CD8 T cells they activate. It is now reported here that interaction of primary CD8 T cells with splenic CD8alpha- DC induced much higher production of IL-3, IFN-gamma and granulocyte-macrophage colony-stimulating factor (GM-CSF), as well as IL-2, than did interaction with CD8alpha+ splenic DC. Furthermore, the CD8alpha- DC also induced higher levels of IL-2, IL-3 and IL-10 production in primary CD4 T cells, compared with that induced by CD8alpha+ DC.

DEC-205 as a marker of dendritic cells with regulatory effects on CD8 T cell responses.

We have previously reported that a population of lymphoid-related CD8alpha(+) DEC-205(+) dendritic cells (DC) from mouse spleen have 'regulatory' effects on the T cells they activate. CD8 T cells produce IL-2 and give a sustained proliferative response to allogeneic CD8alpha(-) DEC-205(-) splenic DC, but produce little IL-2 and give a limited response to allogeneic CD8(+) DEC-205(+) splenic DC. Although CD8alpha and DEC-205 correlate closely among splenic DC, lymph nodes (LN) include a large population of CD8alpha(low) DEC-205(high) DC.

The geometry of synthetic peptide-based immunogens affects the efficiency of T cell stimulation by professional antigen-presenting cells.

In the pathway leading to antibody production there are two points at which CD4(+) T(h) cells need to be recruited. The first of these is priming of T cells by their interaction with dendritic cells (DC) bearing antigen presented on MHC class II molecules and the second is the collaborative interaction of these primed T cells with B cells presenting the same antigen. We have previously shown that the configuration of T and B cell determinants within synthetic peptide immunogens can greatly influence the amount of immunogen required to produce an antibody response.

Does the IL-2 receptor alpha chain induced on dendritic cells have a biological function?

The IL-2 receptor (IL-2R) alpha chain (CD25), but not the IL-2R beta chain, is induced on dendritic cells (DC) by brief periods of culture. To test if this IL-2R alpha is important for DC function, DC were isolated from the spleens of mutant mice with the IL-2R alpha gene disrupted and compared with normal DC for ability to stimulate proliferation of allogeneic CD4 and CD8 T cells in culture. The IL-2R alpha null DC and the normal DC produced nearly identical proliferative responses from CD4 and from CD8 T cells.