Analysis of cytokine secretion by melanoma-specific CD4+ T lymphocytes.
Although specific antitumor immune reactivity has been documented extensively in CD8+ T cells derived from melanoma patients, relatively little is known about CD4+ T cell responses against melanoma. Tumor-infiltrating lymphocytes (TIL) cultured from metastatic lesions in five patients yielded cytolytic CD8+ T cells with specific activity against autologous and MHC class I-compatible allogeneic melanoma targets. In four of the five cases studied, CD4+ T cells purified from bulk TIL cultures also reacted specifically with autologous melanoma cells, as manifested by the secretion of various cytokines (GM-CSF, TNF-alpha, and IFN-gamma) after a 24 h cocultivation. Cytokine secretion by CD4+ T cells was MHC class II restricted, and proved to be a more reliable indicator of the immunologic reactivity of CD4+ T cells than cytolysis. Three of the four reactive CD4+ TIL failed to recognize allogeneic melanomas, suggesting recognition of Ag with limited expression in the patient population. Cloning such Ags may provide clues to optimizing current antitumor immunization strategies.
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
N R
NR
Markus
S A
SA
Rosenberg
S L
SL
Topalian
D000937:Antigen-Antibody Reactions; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006681:HLA-D Antigens / Q000276:immunology; D006801:Humans; D007518:Isoantibodies; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism*; D008545:Melanoma / Q000276:immunology* / Q000378:metabolism / Q000556:secondary; D015203:Reproducibility of Results; D014407:Tumor Cells, Cultured
D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D006681:HLA-D Antigens; D007518:Isoantibodies