Primary antitumor immune response mediated by CD4+ T cells |
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Authors: | Corthay Alexandre Skovseth Dag K Lundin Katrin U Røsjø Egil Omholt Hilde Hofgaard Peter O Haraldsen Guttorm Bogen Bjarne |
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Institution: | Institute of Immunology, University of Oslo, Rikshospitalet and Rikshospitalet University Hospital, 0027 Oslo, Norway. alexandre.corthay@medisin.uio.no |
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Abstract: | Gene-targeted mice have recently revealed a role for lymphocytes and interferon-gamma (IFNgamma) in conferring protection against cancer, but the mechanisms remain unclear. Here, we have characterized a successful primary antitumor immune response initiated by naive CD4+ T cells. Major histocompatibility complex class II (MHC-II)-negative myeloma cells injected subcutaneously into syngeneic mice were surrounded within 3 days by macrophages that captured tumor antigens. Within 6 days, naive myeloma-specific CD4+ T cells became activated in draining lymph nodes and subsequently migrated to the incipient tumor site. Upon recognition of tumor-derived antigenic peptides presented on MHC-II by macrophages, the myeloma-specific CD4+ T cells were reactivated and started to secrete cytokines. T cell-derived IFNgamma activated macrophages in close proximity to the tumor cells. Tumor cell growth was completely inhibited by such locally activated macrophages. These data indicate a mechanism for immunosurveillance of MHC-II-negative cancer cells by tumor-specific CD4+ T cells through collaboration with macrophages. |
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