Critical role of dendritic cells in determining the Th1/Th2 balance upon Leishmania major infection |
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Authors: | Suzue Kazutomo Kobayashi Seiki Takeuchi Tsutomu Suzuki Mamoru Koyasu Shigeo |
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Affiliation: | 1 Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan 2 Department of Parasitology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan 3 Department of Tropical Medicine and Parasitology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan 4 Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Kawaguchi 332-0012, Japan |
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Abstract: | The onset of Th1 immunity is in part regulated by genetic background.To elucidate the cell type carrying critical factors determiningthe Th1 response, we employed Rag-2–/– mice on Leishmaniamajor-susceptible BALB/c and -resistant B10.D2 backgrounds.By using bone marrow (BM) chimeras generated by the transplantationof B10.D2 BM cells into BALB/c-Rag-2–/– mice, andvice versa, it was shown that hematopoietic cells carry factorsdetermining the disease outcome and Th1 response against L.major infection. B10.D2-Rag-2–/– mice reconstitutedwith BALB/c CD4+ T cells exhibited a Th1 response and controlledL. major infection. Wild-type BALB/c mice inoculated with L.major-parasitized B10.D2-Rag-2–/– splenocytes alsoexhibited a Th1 response and a mild disease outcome, whereassuch a Th1 response was not induced when CD11c+ dendritic cells(DCs) were depleted from parasitized B10.D2-Rag-2–/–splenocytes. Th1 response was reconstituted by the additionof L. major-parasitized B10.D2 DCs but not L. major-parasitizedBALB/c DCs to DC-depleted parasitized B10.D2-Rag-2–/–splenocytes. These results indicate that DCs determine the outcomeof the disease upon L. major infection. |
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Keywords: | antigen-presenting cell infectious disease protozoan parasite Th |
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