Characterization of autologous tumor-specific T-helper 2 cells in tumor-infiltrating lymphocytes from a patient with metastatic melanoma

✍ Scribed by Dmitri D. Kharkevitch; Dai Seito; Glen C. Balch; Tomoyuki Maeda; Charles M. Balch; Kyogo Itoh

• Publisher: John Wiley and Sons
• Year: 1994
• Tongue: French
• Weight: 868 KB
• Volume: 58
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.2910580302

✦ Synopsis

Human autologous tumor-specific T-helper 2 (Th2) cells were investigated in melanoma tumor-infiltrating lymphocytes FILS). Both a CD4+ T-cell line and its 5 potential T-cell clones established from TlLs of a patient with metastatic melanoma produced significant levels of IL-4, IL-6, IL-10 and granulocytemacrophage colony-stimulating factor (GM-CSF) in response to autologous, but not any of 12 allogeneic, melanoma cell lines. They also produced IL-3 and IL-8 but not IL-2, IFN-y, TNF-a or TNF-p in response to autologous tumor cells. Furthermore, they showed autologous melanoma-specific cytotoxicity only in an 18-hr 5'Cr-release assay. Specific IL-4, IL-6 or IL-I0 production by the CD4+ M73 T-cell line and its clone was inhibited by anti-class II DR (but not anti-class I) MAb, whereas their specific cytotoxicity was inhibited by anti-class I (but not anti-class II) MAb. Anti-CD3 and -CD4 MAb (but not anti-CD8) abrogated both IL-4, IL6 and IL-I0 production and cytotoxicity, while anti-IL-4 antibody did not inhibit cytotoxicity. CD4+ potential T-cell clones, but not CD8' clones, that were established from freshly isolated TlLs without in vitro sensitization by autologous tumor cells also produced IL-4, IL-6 and IL-10 but not IFN-y or tumor necrosis factor (TNF)a in an autologous tumor-specific fashion. These Th2 cells were neither reactive to EBV-B cells nor suppressive against CD8+ T-cell clones. PMA and PHA stimulated these potential T-cell clones, regardless of their specific lymphokine production, to produce IL-3, IL-4, IL-6, IL-8, IL-10, GM-CSF, TNFa and IFN-y. Our results demonstrate the presence of autologous tumor-specific Th2 cells at the melanoma sites. t 1994 Itilc-lisc, Inc