Characterization of autologous tumor-specific T-helper 2 cells in tumor-infiltrating lymphocytes from a patient with metastatic melanoma.
Human autologous tumor-specific T-helper 2 (Th2) cells were investigated in melanoma tumor-infiltrating lymphocytes (TILs). Both a CD4+ T-cell line and its 5 potential T-cell clones established from TILs of a patient with metastatic melanoma produced significant levels of IL-4, IL-6, IL-10 and granulocyte-macrophage 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-gamma, TNF-alpha or TNF-beta in response to autologous tumor cells. Furthermore, they showed autologous melanoma-specific cytotoxicity only in an 18-hr 51Cr-release assay. Specific IL-4, IL-6 or IL-10 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-10 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 TILs without in vitro sensitization by autologous tumor cells also produced IL-4, IL-6 and IL-10 but not IFN-gamma or tumor necrosis factor (TNF) alpha 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, TNF alpha and IFN-gamma. Our results demonstrate the presence of autologous tumor-specific Th2 cells at the melanoma sites.
Kharkevitch
D D
DD
Department of Surgical Oncology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Seito
D
D
Balch
G C
GC
Maeda
T
T
Balch
C M
CM
Itoh
K
K
D001402:B-Lymphocytes / Q000382:microbiology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D002450:Cell Communication / Q000502:physiology; D002472:Cell Transformation, Viral / Q000502:physiology; D002999:Clone Cells; D016207:Cytokines / Q000096:biosynthesis; D004854:Herpesvirus 4, Human / Q000502:physiology; D006801:Humans; D015847:Interleukin-4 / Q000096:biosynthesis; D016246:Lymphocytes, Tumor-Infiltrating / Q000166:cytology* / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism / Q000473:pathology* / Q000556:secondary*; D012680:Sensitivity and Specificity; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D016207:Cytokines; D015847:Interleukin-4