CD8α+ and CD8α− Subclasses of Dendritic Cells Direct the Development of Distinct T Helper Cells In Vivo

TLDR

Dendritic cells uniquely sensitize naive T cells, and in mice two CD8α‑expressing subclasses differ in localization and function, though their physiological roles remain unclear, with CD8α+ DCs suggested to regulate immunity and CD8α− DCs to be more stimulatory. The authors pulsed CD8α+ and CD8α− DCs with antigen, separated them after overnight GM‑CSF culture, and injected them into syngeneic mice footpads. Both DC subclasses prime antigen‑specific T cells in vivo and steer distinct Th responses—CD8α− DCs promote Th2, CD8α+ DCs promote Th1 via IL‑12—indicating that the presenting DC type dictates adaptive class selection.

Abstract

Cells of the dendritic family display some unique properties that confer to them the capacity to sensitize naive T cells in vitro and in vivo. In the mouse, two subclasses of dendritic cells (DCs) have been described that differ by their CD8α expression and their localization in lymphoid organs. The physiologic function of both cell populations remains obscure. Studies conducted in vitro have suggested that CD8α+ DCs could play a role in the regulation of immune responses, whereas conventional CD8α− DCs would be more stimulatory. We report here that both subclasses of DCs efficiently prime antigen-specific T cells in vivo, and direct the development of distinct T helper (Th) populations. Antigen-pulsed CD8α+ and CD8α− DCs are separated after overnight culture in recombinant granulocyte/macrophage colony-stimulating factor and injected into the footpads of syngeneic mice. Administration of CD8α− DCs induces a Th2-type response, whereas injection of CD8α+ DCs leads to Th1 differentiation. We further show that interleukin 12 plays a critical role in Th1 development by CD8α+ DCs. These findings suggest that the nature of the DC that presents the antigen to naive T cells may dictate the class selection of the adaptative immune response.