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The Journal of Immunology, 2001, 167: 4215-4221.
Copyright © 2001 by The American Association of Immunologists

Induction of CTL and Nonpolarized Th Cell Responses by CD8{alpha}+ and CD8{alpha}- Dendritic Cells1

Géraldine Schlecht, Claude Leclerc and Gilles Dadaglio2

Unité de Biologie des Régulations Immunitaires, Institut Pasteur, Paris, France

Two distinct dendritic cell (DC) subpopulations have been evidenced in mice on the basis of their differential CD8{alpha} expression and their localization 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 II-restricted peptides, we analyzed CD4+ and CD8+ T cell responses obtained after i.v. injection of freshly purified peptide-pulsed DC subsets. First, we showed that both DC subsets efficiently induce specific CTL responses and Th1 cytokine production in the absence of CD4+ T cell priming. Second, we showed that in vivo activation of CD4+ T cells by CD8{alpha}+ or CD8{alpha}- DC, injected i.v., leads to a nonpolarized Th response with production of both Th1 and Th2 cytokines. The CD8{alpha}- subset induced a higher production of Th2 cytokines such as IL-4 and IL-10 than the CD8{alpha}+ subset. However, IL-5 was produced by CD4+ T cells activated by both DC subsets. When both CD4+ and CD8+ T cells were primed by DC injected i.v., a similar pattern of cytokines was observed, but, under these conditions, Th1 cytokines were mainly produced by CD8+ T cells, while Th2 cytokines were produced by CD4+ T cells. Thus, this study clearly shows that CD4+ T cell responses do not influence the development of specific CD8+ T cell cytotoxic responses induced either by CD8{alpha}+ or CD8{alpha}- DC subsets.




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