antigen presenting cell, CD4+ T lymphocyte, cell differentiation, dendritic cell, Leishmania major, protozoal proteins
Interferon (IFN)-γ, a cytokine critical for resistance to infection and tumors, is produced by CD4+ helper T lymphocytes after stimulation by cultured dendritic cells (DCs) that secrete a cofactor, interleukin (IL)-12. We have identified a major IL-12-independent pathway whereby DCs induce IFN-γ-secreting T helper (Th)1 CD4+ T cells in vivo. This pathway requires the membrane-associated tumor necrosis family member CD70 and was identified by targeting the LACK antigen from Leishmania major within an antibody to CD205 (DEC-205), an uptake receptor on a subset of DCs. Another major DC subset, targeted with 33D1 anti-DCIR2 antibody, also induced IFN-γ in vivo but required IL-12, not CD70. Isolated CD205 + DCs expressed cell surface CD70 when presenting antigen to T cell receptor transgenic T cells, and this distinction was independent of maturation stimuli. CD70 was also essential for CD205+ DC function in vivo. Detection of the IL-12-independent IFN-γ pathway was obscured with nontargeted LACK, which was presented by both DC subsets. This in situ analysis points to CD70 as a decision maker for Th1 differentiation by CD205+ DCs, even in Th2-prone BALB/c animals and potentially in vaccine design. The results indicate that two DC subsets have innate propensities to differentially affect the Th1/Th2 balance in vivo and by distinct mechanisms.
Soares, H., H. Waechter, N. Glaichenhaus, E. Mougneau, H. Yagita, O. Mizenina, D. Dudziak, M. C. Nussenzweig, and R. M. Steinman. 2007. "A Subset of Dendritic Cells Induces CD4+ T Cells to Produce IFN-γ by an IL-12-Independent but CD70-Dependent Mechanism in Vivo." Journal of Experimental Medicine 204 (5): 1095-1106