Studies on regulatory mechanism of Th1/Th2 cell differentiation by antigen presenting cell (APC) and onAPC-mediated immunotherapy

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Regulatory mechanisms of Th1/Th2 cell differentiation by antigen presenting cell (APC) and APC-mediated immunotherapy were investigated for 3 years (from 2004 to 2007) and following results were obtained.1) Th1/Th2 cell differentiation in certain diseases, such as murine babesiosis, and canine malignant melanoma and histiocytic sarcoma:a) IL-12p70 production from APC (included splenic macrophages) induced Th1 cell differentiation and closely related to transient parasitemia in Babesia microti infection. IL-12p70 was suggested to be an important factor for eliminating Babesia microti.b) Seven novel cell lines from canine histiocytic sarcoma were established. All of them showed phagocytic and processing activities, suggesting to be a mononuclear phagocytic system cell and also APC.2) Stimulatory factors for Th1/Th2 cell differentiation:a) Stimulatory factors for IL-12 production, by which Th1 cell differentiation was introduced, from macrophages were isolated and purified from culture medium of Babesia microti and Babesia rodhaini infected erythrocytes. These factors were heat stable and soluble and their elution profiles were quite different between Babesia microti and Babesia rodhaini cultured medium.3) APC-mediated immunotherapya) Against canine malignant melanoma: Canine APC from bone marrow were pulsed with lysate o canine melanoma cell lines and were transplanted into clinically healthy dogs. APC induced cell-mediated immunological responses against melanoma cells and prolonged survival period.b) Against Babesia microti and Babesia rodhaini. Murine bone marrow-derived APC pulsed with Babesia microti infected erythrocytes induced decrease of parasitemia and increased survival rate in mice infected with Babesia rodhaini. These results suggested that APC-mediated therapy is an available manner for protozoan and cancer diseases.