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.
Markus
N R
NR
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Rosenberg
S A
SA
Topalian
S L
SL
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