CD8 alpha(-) and CD8 alpha(+) subclasses of dendritic cells undergo phenotypic and functional maturation in vitro and in vivo

Dendritic cells (DCs) are essential for the priming of immune responses. Th is antigen-presenting function of DCs develops in sequence in a process cal led maturation, during which they become potent sensitizers of naive T cell s but reduce their ability to capture and process antigens, Some heterogene ity exists in mouse-DC populations, and two distinct subsets of DCs express ing high levels of CD11c can be identified on the basis of CD8 alpha expres sion. We have studied the phenotype and maturation state of mouse splenic C D8 alpha (-) and CD8 alpha (+) DCs. Both subsets were found to reside in th e spleen as immature cells and to undergo a phenotypic maturation upon cult ure in vitro in GM-CSF-containing medium or in. vivo in response to lipopol ysaccharide. In vitro and in vivo analyses showed that this maturation proc ess is an absolute requisite for DCs to acquire their T-cell priming capaci ty, transforming CD8 alpha (-) and CD8 alpha (+) DCs into potent and equall y efficient activators of naive CD4(+) and CD8(+) T cells, Furthermore, the se results highlight the importance that environmental factors may have on the ability of DC subsets to influence Th responses qualitatively; i.e,, th e ability to drive Th1 versus Th2 differentiation may not be fixed immutabl y for each DC subset.