CD4+ and CD8+ cytotoxic T‐cell (CTL) clones, selected for T‐ceII‐receptor (TcR)‐dependent lysis of the autologous tumor and isolated from peripheral‐blood lymphocytes (PBL) or tumor‐infiltrating lymphocytes (TIL) of 3 melanoma patients, were characterized for the pattern of 13 different cytokines released by antibody‐ or tumor‐mediated triggering. Induction or enhancement of cytokine release by anti‐CD3 monoclonal antibody (MAb) led to the identification of 2 major sub‐sets of CD8+ CTL clones on the basis of production of IL‐4. Within the 2 groups of IL‐4‐producing or non‐producing clones, further sub‐sets could be identified on the basts of differential production of IL‐1 p, IL‐2, IL‐6, IL‐8, IL‐10, TNF‐α, TNF β and IFN‐γ. A similar analysis performed on a panel of CD4+ CTL clones indicated multiple patterns consistent with at least 4 major sub‐sets, but further complexity was evident in each sub‐set on the basis of differential production of IL‐1, IL2, IL‐6, IL‐10 and G‐CSF. The cytokine profile of CD4+ and CD8+ clones, as determined after anti‐CD3 stimulation, was different from the pattern seen after co‐culture with autologous tumor, since many clones released cytokines such as IL‐4, IL‐10, IFN‐α and‐β, TNF‐γ and GM‐CSF after activation with only 1 of the 2 stimuli. These results indicate that CD4+ and CD8+ CTL clones reacting to human melanoma belong to a highly complex repertoire of functional subsets characterized by distinct cytokine profiles. In addition, the cytokine pattern of each T‐cell sub‐set can be modulated by changing the activation signals delivered to the T cell. © Wiley‐Liss, Inc.
ASJC Scopus subject areas
- Cancer Research