title: Critical role of dendritic cells in determining the Th1/Th2 balance upon Leishmania major infection.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Kazutomo
authors.initials: K
authors.lastname: Suzue
authors.forename: Seiki
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Takeuchi
authors.forename: Mamoru
authors.initials: M
authors.lastname: Suzuki
authors.forename: Shigeo
authors.initials: S
authors.lastname: Koyasu
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology / Q000469:parasitology; D002478:Cells, Cultured; D002678:Chimera / Q000276:immunology / Q000469:parasitology; D003713:Dendritic Cells / Q000276:immunology* / Q000469:parasitology; D007113:Immunity, Innate / Q000235:genetics*; D018320:Leishmania major / Q000276:immunology*; D007896:Leishmaniasis / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*