Dendritic cells as stimulator cells of MHC class I-restricted immune responses

Abstract

We have shown that growth factor-dependent, MHC class I+/II dendritic cell lines established from mouse fetal skin, can stimulate naive, allogeneic but not syngeneic CD8+ T cells in the absence of CD4+ T cells and that this T cell response is restricted by MHC class I molecules. We further showed that the FSCL-induced activation of naive CD8+ T cells is critically dependent on the physical contact between stimulator and responder cells and the expression of the costimulatory molecule B7 on FSCL. An important question that remains to be addressed concerns the derivation of FSCL. One could argue that they are members of the LC/DC family because they (i) exhibit certain features of fetal murine LC (i.e., CD45+, CD44+, CD32+, MHC class I+, MHC class II-, asialo GM1+, TCR-) including membrane-bound ADPase activity (A. Elbe, unpublished observation) and (ii) exhibit a pronounced dendritic configuration when cultured. If these cells are indeed derived from fetal LC, they should undergo the same phenotypic changes (MHC class II(-)-->MHC class II+) under in vitro culture conditions as do fetal LC in situ. However, our FSCL are phenotypically stable, and attempts to induce MHC class II expression with cytokine cocktails were unsuccessful. One explanation for this phenomenon could be that stimulatory signals provided by fetal keratinocytes or other skin cells are responsible for LC maturation in vivo and that, due to the early demise of these "stromal" cells in fetal skin cell cultures, the maturation process would not have been completed.(ABSTRACT TRUNCATED AT 250 WORDS)