Human melanoma-specific, noncytolytic CD8+ T cells that can synthesize type I cytokine.
The existence of CD8+ CTLs that are capable of recognizing MHC class I-bound, human tumor-associated peptide antigens is now unequivocally documented in cancer patients. Thus far, the role of CD8+ T cells in tumor immunity has been predominantly viewed in terms of cytolytic ability as the prime mode of their function. Interestingly, it is increasingly evident that CD8+ T cells are capable of synthesizing both type I and type II cytokines. Thus, it is conceivable that tumor antigen-specific but noncytolytic CD8+ T cells might play an important role in antitumor immune response by synthesizing type I cytokine. Through such cytokines, they could provide "help" for the process of generating as well as in maintaining an effective CD8+ CTL response. In addition, they might recruit other types of effector cells (such as natural killer cells, macrophages, and others) locally at the tumor site. Either way, they could exert a profoundly positive role in cell-mediated antitumor immune response, particularly because the great majority of tumor cells express only MHC class I molecules that present peptide epitopes to CD8+ T cells. Unfortunately, tumor antigen-specific, noncytolytic but type I cytokine-secreting CD8+ T cells have not received much investigative attention. Here we show that CD8+ T cells, isolated from the tumor-infiltrating lymphocytes from human melanoma, synthesize type I cytokine (IFN-gamma and tumor necrosis factor alpha) in a MHC class I-restricted and tumor-specific noncytolytic interaction with the autologous melanoma cells.
Chakraborty
N G
NG
University of Connecticut School of Medicine, Farmington 06030, USA.
Mukherji
B
B
D000951:Antigens, Neoplasm / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D008198:Lymph Nodes / Q000473:pathology; D008545:Melanoma / Q000276:immunology*; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins / Q000276:immunology*; D012680:Sensitivity and Specificity; D018417:Th1 Cells / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D016207:Cytokines; D007375:Interleukin-1; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins