CHARACTERIZATION AND AUGMENTATION OF CD4-CELL LINES AGAINST MELANOMA(CYTOTOXIC T)

Cytotoxic T cells have been implicated in the control of the progressi on of human melanoma. Most studies on human tumor T cell immunity have focused on the CD3(+)CD8(+) cytotoxic T lymphocyte (CTL) phenotype; h owever, CD3(+)CD4(+) CTL are important effector cells in other disease s and may also contribute to antimelanoma immunity. In this study we c ompared the functional activity of CD3(+)CD4(+) and CD3(+)CD8(+) CTL l ines generated against autologous melanoma cells. CD8(+) CTL had twofo ld higher cytotoxicity and serine esterase activity than CD4(+) CTL. C D8(+) CTL also were better binders to autologous melanoma cells. Bindi ng of both CD4(+) and CD8(+) CTL to melanoma cells was significantly i nhibited by ICAM-1 mAb. Interleukin-2 (IL-2) and IL-4 secretion was in duced in both CD4(+) and CD8(+) CTL after stimulation by melanoma cell s. A reverse transcriptase polymerase chain reaction performed on spec ific messenger RNA showed that both CD4(+) and CD8(+) CTL expressed IL -1, IL-2 and IL-4; CD4(+) CTL also expressed interferon gamma (IFN). B oth 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 co mbination of IL-2, IL-4 and IFN provided the optimal stimulation. Trea tment of melanoma target cells with IL-4 and IFN enhanced CD4(+) CTL r ecognition 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 i mmunity.