B7-2 expressed on EL4 lymphoma suppresses antitumor immunity by an interleukin 4-dependent mechanism

For T cells to become functionally activated they require at least two sign als. The B7 costimulatory molecules B7-1 and B7-2 provide the "second signa l" pivotal for T cell activation. In this report, we studied the relative r oles of B7-1 and B7-2 molecules in the induction of antitumor immunity to t he T cell thymoma, EL4. We generated EL4 tumor cells that expressed B7-1, B 7-2, and B7-1+B7-2 by transfecting murine cDNAs. Our results demonstrate th at EL4-B7-1 cells are completely rejected in syngeneic mice. Unlike EL4-B7- 1 cells, we fmd that EL4-B7-2 cells are not rejected but progressively grow in the mice. A B7-1- and B7-2-EL4 double transfectant was generated by int roducing B7-2 cDNA into the EL4-B7-1 tumor line that regressed in vivo. The EL4-B7-1+B7-2 double transfectant was not rejected when implanted into syn geneic mice but progressively grew to produce tumors. The double transfecta nt EL4 cells could costimulate T cell proliferation that could be blocked b y anti-B7-1 antibodies, anti-B7-2 antibodies, or hCTLA4 immunoglobulin, sho wing that the B7-1 and B7-2 molecules expressed on the EL4 cells were funct ional. In vivo, treatment of mice implanted with double-transfected EL4 cel ls with anti-B7-2 monoclonal antibody resulted in tumor rejection. Furtherm ore, the EL4-B7-2 and EL4-B7-1+B7-2 cells, but not the wild-type EL4 cells, were rejected in interleukin 4 (IL-4) knockout mice. Our data suggests tha t B7-2 expressed on some T cell tumors inhibits development of antitumor im munity, and IL-4 appears to play a critical role in abrogation of the antit umor immune response.