Dendritic cells lose ability to present protein antigen after stimulating antigen-specific T cell responses, despite upregulation of MHC class II expression

Immature dendritic cells (DC) take up, process and present protein antigens ; mature DC are specialized for stimulating primary T cell responses with i ncreased expression of MHC class II and co-stimulatory molecules, but are i ncapable of processing and presenting soluble protein. The current study ex amined whether maturation of DC is triggered by T cell recognition of antig ens presented by immature DC. Human DC derived from CD34(+) progenitor cell s by culture with granulocyte macrophage colony-stimulating factor (GM-CSF) and interleukin-6 (IL-6) in serum-free medium could prime naive CD4(+) T c ells to keyhole limpet hemocyanin (KLH) and ovalbumin (OVh). The cultured D C retained the ability to prime T cells to native protein for at least 15 d ays. To test for changes in DC function after participation in an immune re sponse, DC were co-cultured with either allogeneic or autologous CT4(+) T c ells. DC co-cultured with autologous T cells retained the ability to prime T cells to intact protein antigens. By contrast, DC which had previously st imulated an allogeneic T cell response lost ability to prime T cells to sol uble proteins. However, such much less than T cell-activated DC much greate r than induced a MLR and stimulated peptide-specific primary CD4(+) T cell responses. This indicated that much less than T cell-activated DC much grea ter than did not die or lose the ability to prime, but lost the ability to process and present subsequent antigens. Following participation in T cell activation, DC increased surface expression of MHC class II, co-stimulatory molecules CD40 and B7.2, and the intercellular adhesion molecule-1 (ICAM-1 ). In addition, our data suggest that interferon gamma (IFN-gamma) and tumo r necrosis factor alpha (TNF-alpha) are involved in this T cell-mediated DC maturation.