Characterization and augmentation of CD4+ cytotoxic T cell lines against melanoma.
Cytotoxic T cells have been implicated in the control of the progression of human melanoma. Most studies on human tumor T cell immunity have focused on the CD3+CD8+ cytotoxic T lymphocyte (CTL) phenotype; however, CD3+CD4+ CTL are important effector cells in other diseases and may also contribute to antimelanoma immunity. In this study we compared the functional activity of CD3+CD4+ and CD3+CD8+ CTL lines generated against autologous melanoma cells. CD8+ CTL had twofold higher cytotoxicity and serine esterase activity than CD4+ CTL. CD8+ CTL also were better binders to autologous melanoma cells. Binding of both CD4+ and CD8+ CTL to melanoma cells was significantly inhibited by ICAM-1 mAb. Interleukin-2 (IL-2) and IL-4 secretion was induced in both CD4+ and CD8+ CTL after stimulation by melanoma cells. A reverse transcriptase polymerase chain reaction performed on specific messenger RNA showed that both CD4+ and CD8+ CTL expressed IL-1, IL-2 and IL-4; CD4+ CTL also expressed interferon gamma (IFN). Both CTL phenotypes expressed receptors for IL-2 and IFN but only CD4+ CTL expressed the receptor for IL-4. Methods to augment CD4+ CTL growth were assessed using different combinations of cytokines. The combination of IL-2, IL-4 and IFN provided the optimal stimulation. Treatment of melanoma target cells with IL-4 and IFN enhanced CD4+ CTL recognition activity. CD4+ T cells are associated with antigen memory response and helper function, therefore activation of CD4+ CTL may be more beneficial with respect to long-term protective antimelanoma immunity.
Morisaki
T
T
John Wayne Cancer Institute at Saint John's Hospital and Health Center, Santa Monica, CA 90404.
Morton
D L
DL
Uchiyama
A
A
Yuzuki
D
D
Barth
A
A
Hoon
D S
DS
D001483:Base Sequence; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D016207:Cytokines / Q000494:pharmacology / Q000502:physiology; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D004950:Esterases / Q000097:blood; D006801:Humans; D007167:Immunotherapy; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008545:Melanoma / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D008969:Molecular Sequence Data; D010641:Phenotype; D018121:Receptors, Cytokine / Q000502:physiology; D014407:Tumor Cells, Cultured
D016207:Cytokines; D007376:Interleukin-2; D018121:Receptors, Cytokine; D015847:Interleukin-4; D004950:Esterases; C022635:serine esterase