Critical role of dendritic cells in determining the T_h 1/T_h2 balance upon Leishmania major infection

The onset of T_h1 immunity is in part regulated by genetic background. To elucidate the cell type carrying critical factors determining the T_h1 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_h1 response against L. major infection. B10.D2-Rag-2^-/- mice reconstituted with BALB/c CD4⁺ T cells exhibited a T_h1 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_h1 response and a mild disease outcome, whereas such a T_h1 response was not induced when CD11c⁺ dendritic cells (DCs) were depleted from parasitized B10.D2-Rag-2^-/- splenocytes. T_h1 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.