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 tumours and further active immunity against the non-transfected tumour. We therefore asked to what level similarly induced expression of B7 on human melanoma cells would affect the antigen-dependent responses of tumour-specific T cell clones in vitro. Data presented show that B7-1 expression 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 TNF responses of all the CD4+ clones. However, despite these clear co-stimulatory effects on antigen-induced responses of all T cell clones, which demonstrated an effective interaction of the B7-1 transfected molecule 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 secretion exhibited by many of these clones in response to in vitro antigen presentation by melanoma cells. We further show that defective IL-2 secretion in response to melanoma antigens was not due to a T cell clone refractoriness induced by the culture, since one of these clones could be induced to secrete IL-2 by an antigen-expressing melanoma line, upon increased lymphocyte function associated antigen-3 expression induced by gene transfection. Together these data suggest that defective IL-2 secretion by many tumour-infiltrating lymphocytes clones in response to antigen presentation by melanoma cells in vitro is not exclusively due to the inability of these cells to provide an appropriate co-stimulation through the B7-1 molecule.
Viret
C
C
U211 INSERM, Institut de Biologie, Faculté des sciences de Nantes, France.
Gervois
N
N
Guilloux
Y
Y
Le Dréan
E
E
Diez
E
E
Jotereau
F
F
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D018122:B7-1 Antigen / Q000235:genetics / Q000502:physiology*; D018106:CD28 Antigens / Q000276:immunology; D018968:CD58 Antigens / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D002999:Clone Cells; D005354:Fibrosarcoma; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism*; D008213:Lymphocyte Activation; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008545:Melanoma / Q000276:immunology* / Q000473:pathology; D051379:Mice; D009363:Neoplasm Proteins / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D014162:Transfection
D000911:Antibodies, Monoclonal; D018122:B7-1 Antigen; D018106:CD28 Antigens; D018968:CD58 Antigens; D007376:Interleukin-2; D009363:Neoplasm Proteins; D011993:Recombinant Fusion Proteins