Development of antigen-specific CD8+ CTL in MHC class I-deficient mice through CD4 to CD8 conversion |
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Authors: | Tanaka Yasuhiro Koido Shigeo Xia Jianchuan Ohana Masaya Liu Chunlei Cote Gregory M Sawyer Douglas B Calderwood Stuart Gong Jianlin |
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Institution: | Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA. |
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Abstract: | CD8+ CTL are the predominant tumoricidal effector cells. We find, however, that MHC class I-deficient mice depleted of CD8+ T cells are able to mount an effective antitumor immunity after immunization with fused dendritic/tumor cells. Such immunity appears to be mediated by the generation of phenotypic and functional CD8+ CTL through CD4+ to CD8+ conversion, which we have demonstrated at the single cell level. CD4+ to CD8+ conversion depends on effective in vivo activation and is promoted by CD4+ T cell proliferation. The effectiveness of this process is shown by the generation of antitumor immunity through adoptive transfer of primed CD4 T cells to provide protection against tumor cell challenge and to eliminate established pulmonary metastases. |
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