title: Multiple sub-sets of CD4+ and CD8+ cytotoxic T-cell clones directed to autologous human melanoma identified by cytokine profiles.
abstract: CD4+ and CD8+ cytotoxic T-cell (CTL) clones, selected for T-cell-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 basis of differential production of IL-1 beta, IL-2, IL-6, IL-8, IL-10, TNF-alpha, TNF beta and IFN-gamma. 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-alpha and -gamma, TNF-alpha 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.
authors.affiliation: Division of Experimental Oncology D, Istituto Nazionale Tumori, Milan, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Maccalli
authors.forename: R
authors.initials: R
authors.lastname: Mortarini
authors.forename: G
authors.initials: G
authors.lastname: Parmiani
authors.forename: A
authors.initials: A
authors.lastname: Anichini
mesh_terms: D000911:Antibodies, Monoclonal; D017252:CD3 Complex / Q000276:immunology; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D016827:CD8 Antigens / Q000276:immunology*; D002999:Clone Cells; D016207:Cytokines / Q000096:biosynthesis* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006133:Growth Substances / Q000096:biosynthesis* / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000473:pathology; D008545:Melanoma / Q000097:blood* / Q000276:immunology* / Q000473:pathology; D016176:T-Lymphocyte Subsets; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D016827:CD8 Antigens; D016207:Cytokines; D006133:Growth Substances