Induction of CTL and nonpolarized Th cell responses by CD8 alpha(+) and CD8 alpha(-) dendritic cells

Two distinct dendritic cell (DQ subpopulations have been evidenced in mice on the basis of their differential CD8 alpha expression and their localizat ion in lymphoid organs. Several reports suggest that CD8 alpha (+) and CD8 alpha (-) DC subsets could be functionally different. In this study, using a panel of MHC class I- and/or class If-restricted peptides, we analyzed CD 4(+) and CD8(+) T cell responses obtained after Lv. injection of freshly pu rified peptide-pulsed DC subsets. First, we showed that both DC subsets eff iciently induce specific CTL responses and Th1 cytokine production in the a bsence of CD4(+) T cell priming. Second, we showed that in vivo activation of CD4(+) T cells by CD8 alpha (+) or CD8 alpha (-) DC, injected 1.v., lead s to a nonpolarized Th response with production of both Th1 and Th2 cytokin es. The CD8 alpha (-) subset induced a higher production of Th2 cytokines s uch as IL-4 and IL-10 than the CD8 alpha (+) subset. However, IL-5 was prod uced by CD4(+) T cells activated by both DC subsets. When both CD4(+) and C D8(+) T cells were primed by DC injected i.v., a similar pattern of cytokin es was observed, but, under these conditions, Th1 cytokines were mainly pro duced by CD8(+) T cells, while Th2 cytokines were produced by CD4(+) T cell s. Thus, this study clearly shows that CD4(+) T cell responses do not influ ence the development of specific CD8(+) T cell cytotoxic responses induced either by CD8 alpha (+) or CD8 alpha (-) DC subsets.