Critical role of dendritic cells in determining the Th1/Th2 balance upon Leishmania major infection.

The onset of T(h)1 immunity is in part regulated by genetic background. To elucidate the cell type carrying critical factors determining the T(h)1 response, we employed Rag-2(-/-) mice on Leishmania major-susceptible BALB/c and -resistant B10.D2 backgrounds. By using bone marrow (BM) chimeras generated by the transplantation of B10.D2 BM cells into BALB/c-Rag-2(-/-) mice, and vice versa, it was shown that hematopoietic cells carry factors determining the disease outcome and T(h)1 response against L. major infection. B10.D2-Rag-2(-/-) mice reconstituted with BALB/c CD4(+) T cells exhibited a T(h)1 response and controlled L. major infection. Wild-type BALB/c mice inoculated with L. major-parasitized B10.D2-Rag-2(-/-) splenocytes also exhibited a T(h)1 response and a mild disease outcome, whereas such a T(h)1 response was not induced when CD11c(+) dendritic cells (DCs) were depleted from parasitized B10.D2-Rag-2(-/-) splenocytes. T(h)1 response was reconstituted by the addition of L. major-parasitized B10.D2 DCs but not L. major-parasitized BALB/c DCs to DC-depleted parasitized B10.D2-Rag-2(-/-) splenocytes. These results indicate that DCs determine the outcome of the disease upon L. major infection.