Complementary Dendritic Cell–activating Function of CD8(+) and CD4(+) T Cells: Helper Role of CD8(+) T Cells in the Development of T Helper Type 1 Responses

Dendritic cells (DCs) activated by CD40L-expressing CD4(+) T cells act as mediators of “T helper (Th)” signals for CD8(+) T lymphocytes, inducing their cytotoxic function and supporting their long-term activity. Here, we show that the optimal activation of DCs, their ability to produce high levels of bioactive interleukin (IL)-12p70 and to induce Th1-type CD4(+) T cells, is supported by the complementary DC-activating signals from both CD4(+) and CD8(+) T cells. Cord blood– or peripheral blood–isolated naive CD8(+) T cells do not express CD40L, but, in contrast to naive CD4(+) T cells, they are efficient producers of IFN-γ at the earliest stages of the interaction with DCs. Naive CD8(+) T cells cooperate with CD40L-expressing naive CD4(+) T cells in the induction of IL-12p70 in DCs, promoting the development of primary Th1-type CD4(+) T cell responses. Moreover, the recognition of major histocompatibility complex class I–presented epitopes by antigen-specific CD8(+) T cells results in the TNF-α– and IFN-γ–dependent increase in the activation level of DCs and in the induction of type-1 polarized mature DCs capable of producing high levels of IL-12p70 upon a subsequent CD40 ligation. The ability of class I–restricted CD8(+) T cells to coactivate and polarize DCs may support the induction of Th1-type responses against class I–presented epitopes of intracellular pathogens and contact allergens, and may have therapeutical implications in cancer and chronic infections.