B7.1 gene transduction of human renal-cell-carcinoma cell lines restores the proliferative response and cytotoxic function of allogeneic T cells.
Renal-cell-carcinoma is one of the human tumors for which the immune response may control the growth of tumor cells. Conversely, T cells infiltrating this tumor have been reported to be impaired in proliferative and effector functions. Complete activation of T cells requires 2 signaling events, one through the antigen-specific receptor and one through the B7 ligand, CD28. In the present study, we first showed the absence of B7.1 expression on RCC tumors and cell lines, and the low proliferative response of allogeneic T cells upon stimulation with these cells. Transduction of the human gene for B7.1 rendered these cells potent stimulators of allogeneic mixed lymphocyte response. Furthermore, stimulation of purified CD4+ and CD8+ T-cell populations showed that transduced cell lines preferentially induced the proliferation of CD8+ T cells. Finally, mixed lymphocyte cultures in the presence of the B7.1+ cell lines led to the generation of cytotoxic T lymphocytes able to specifically recognize both the transduced stimulator and the parental cell line. We thus demonstrate that B7.1 expression on human tumor cell lines is capable of inducing MHC-class-I-dependent proliferation and differentiation into cytotoxic effectors of allogeneic CD8+ T cells. The lack of B7 expression on RCC cell lines is responsible for their failure to activate allogeneic T cells, a result which strongly suggests that the same mechanism may be implied in the impaired tumor-cell presentation to autologus T cells.
Bain
C
C
Département de Biologie des Tumeurs, Centre Léon Bérard, Lyon, France.
Merrouche
Y
Y
Puisieux
I
I
Duc
A
A
Colombo
M P
MP
Favrot
M
M
D018122:B7-1 Antigen / Q000235:genetics* / Q000276:immunology; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D002455:Cell Division / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics* / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D018122:B7-1 Antigen; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II