Spleen-Resident CD4.sup.+ and CD4.sup.- CD8[alpha].sup.- Dendritic Cell Subsets Differ in Their Ability to Prime Invariant Natural Killer T Lymphocytes

One important function of conventional dendritic cells (cDC) is their high capacity to capture, process and present Ag to T lymphocytes. Mouse splenic cDC subtypes, including CD8[alpha].sup.+ and CD8[alpha].sup.- cDC, are not identical in their Ag presenting and T cell priming functions. Surprisingly, few studies have reported functional differences between CD4.sup.- and CD4.sup.+ CD8[alpha].sup.- cDC subsets. We show that, when loaded in vitro with OVA peptide or whole protein, and in steady-state conditions, splenic CD4.sup.- and CD4.sup.+ cDC are equivalent in their capacity to prime and direct CD4.sup.+ and CD8.sup.+ T cell differentiation. In contrast, in response to [alpha]-galactosylceramide ([alpha]-GalCer), CD4.sup.- and CD4.sup.+ cDC differentially activate invariant Natural Killer T (iNKT) cells, a population of lipid-reactive non-conventional T lymphocytes. Both cDC subsets equally take up [alpha]-GalCer in vitro and in vivo to stimulate the iNKT hybridoma DN32.D3, the activation of which depends solely on TCR triggering. On the other hand, and relative to their CD4.sup.+ counterparts, CD4.sup.- cDC more efficiently stimulate primary iNKT cells, a phenomenon likely due to differential production of co-factors (including IL-12) by cDC. Our data reveal a novel functional difference between splenic CD4.sup.+ and CD4.sup.- cDC subsets that may be important in immune responses.