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Development of Antigen-Specific CD8⁺ CTL in MHC Class I-Deficient Mice through CD4 to CD8 Conversion¹

Yasuhiro Tanaka^2,*, Shigeo Koido^2,*, Jianchuan Xia^2,*,, Masaya Ohana, Chunlei Liu, Gregory M. Cote, Douglas B. Sawyer, Stuart Calderwood and Jianlin Gong^3,*,,

^* Dana-Farber Cancer Institute and Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115; and Department of Medicine, Boston University School of Medicine, Boston, MA 02118

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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