The Generation of CD4 Cytotoxic T Lymphocyte Augmented by Immobilized Anti-CD3 Antibody and Interleukin-2

Abstract

The DNA synthesis and the proliferative response of autologous tumor specific cytotoxic T lymphocytes (CTLs) induced by autologous mixed lymphocyte tumor cell culture, remarkably increased by activation with immobilized anti-CD3 Ab and IL-2 compared with IL-2 alone. The cytotoxicity of the activated CTLs was kept against autologous tumor cells, moreover was induced against KATO-III and Daudi. The cytotoxicity was inhibited by anti-HLA class I and anti-HLA-DR MoAb in 4-h CRA and anti-HLA-DR MoAb in 16-h CRA against autologous tumor cells. In addition, the cytotoxicity was inhibited by the elimination of CD8+ cells for 4 h and that of CD4+ cells in 16-h CRA using negative selection against autologous tumor cells. Major cell surface antigens of these CTLs was CD3+, CD4+ CD25+ CD45RA-, helper T cell, and the activated CTLs which produced IL-2. It is concluded that the CTLs activated with immobilized anti-CD3 Ab and IL-2 were CD4+ CTLs having not only killer function but helper function and were one of the effective strategies in adoptive immunotherapy by the direct cytotoxicity and the induction of killer cells in vivo.