Generation of CD4+ cytotoxic T lymphocytes stimulated by immobilized anti-CD3 monoclonal antibody and interleukin-2 in cancer patients.
The proliferation of autologous tumor-reactive cytotoxic T lymphocytes (CTL), induced by autologous mixed lymphocyte tumor-cell culture, was remarkably enhanced by activation with immobilized anti-CD3 monoclonal antibody (MAb) and interleukin-2 (IL-2), as compared with IL-2 alone. The activated CTL exhibited high cytotoxicity against autologous tumor cells. Cytotoxicity against autologous tumor cells was inhibited by anti-HLA-DR MAb. In negative selection with immunomagnetic beads, cytotoxicity against autologous tumor cells was inhibited by the elimination of CD4+ cells. The major cell-surface antigens of the activated CTL were CD3+, CD4+, CD25+, CD45RO+ and CD45RA-, suggesting helper T cells, and the activated CTL produced IL-2. It is concluded that the CTL activated by immobilized anti-CD3 MAb and IL-2 were CD4 cells that had both killer and helper functions. Our findings indicate that adoptive immunotherapy using these activated CTL would be effective in cancer patients.
Tani
M
M
Department of Gastroenterological Surgery, Wakayama Medical School, Japan.
Tanimura
H
H
Yamaue
H
H
Mizobata
S
S
Iwahashi
M
M
Tsunoda
T
T
Noguchi
K
K
Tamai
M
M
Hotta
T
T
Terasawa
H
H
D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D017252:CD3 Complex / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D002455:Cell Division; D003602:Cytotoxicity, Immunologic; D006801:Humans; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000494:pharmacology*; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex / Q000276:immunology; D009369:Neoplasms / Q000276:immunology*
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D007376:Interleukin-2