T-CELL ACTIVATION BY ANTIGENS ON HUMAN-MELANOMA CELLS - CO-STIMULATION BY B7-1 IS NEITHER SUFFICIENT NOR NECESSARY TO STIMULATE IL-2 SECRETION BY MELANOMA-SPECIFIC T-CELL CLONES IN-VITRO

B7-1 expression, induced by transfection in poorly immunogenic murine tumours, was shown to elicit a T cell-mediated rejection of these tumo urs and further active immunity against the nontransfected tumour. We therefore asked to what level similarly induced expression of B7 on hu man melanoma cells would affect the antigen-dependent responses of tum our-specific T cell clones in vitro. Data presented show that B7-1 exp ression by melanoma lines: (i) significantly induced, or improved, an IL-2-dependent proliferative response of such clones to the antigen; ( ii) increased the amount of IL-2 produced by two clones in response to the parental non-transfected tumour cells; and (iii) increased the TN F responses of all the CD4(+) clones. However, despite these clear cc- stimulatory effects on antigen-induced responses of all T cell clones, which demonstrated an effective interaction of the B7-1 transfected m olecule with one or the other of its counter-receptors expressed on T cell clones, B7 co-stimulation did not correct the defect of IL-2 secr etion exhibited by many of these clones in response to in vitro antige n presentation by melanoma cells. We further show that defective IL-2 secretion in response to melanoma antigens was not due to a T cell clo ne refractoriness induced by the culture, since one of these clones co uld be induced to secrete IL-2 by an antigen-expressing melanoma line, upon increased lymphocyte function associated antigen-3 expression in duced by gene transfection. Together these data suggest that defective IL-2 secretion by many tumour-infiltrating lymphocytes clones in resp onse to antigen presentation by melanoma cells in vitro is not exclusi vely due to the inability of these cells to provide an appropriate co- stimulation through the B7-1 molecule.