Protective immunity induced by B7/CD28-costimulated γ δ T cells to the EL-4 lymphoma in allogenic athymic mice

Abstract

We previously reported that the murine EL-4 lymphoma (H-2b) transduced with a retrovirus containing the murine B7-1 gene (B7+ EL-4) grew transiently for several weeks and subsequently regressed in allogenic BALB/c (nu/nu) athymic mice (H-2d). We now show that, in contrast, B7+ EL-4 cells grow progressively in several combined immunodeficiency mice, including SCID and NIH III mice, which lack T cells expressing either TCR-α β or -γ δ. Furthermore, depletion of γ δ T cells with a specific mAb made possible the progressive growth of B7+ EL-4 cells in 90% of athymic mice while depletion of α β T cells allowed tumor growth in 50% of these mice. Immunization of athymic mice with B7+ EL-4 cells prevented the outgrowth of wild-type B7- EL-4 cells. This protective immunity was abrogated by in vivo treatment with an anti-TCR-γ δ mAb, further indicating that γ δ T cells play an important role in tumor rejection by athymic mice. A γ δ T cell line, Tc1, was established from B7+ EL-4-immunized athymic mice by repeated restimulation in vitro with irradiated B7+ EL-4 cells. When tested against a broad spectrum of target cells, Tc1 lysed several murine lymphoma lines, but did not lyse other tumor lines, suggesting that the Ag recognized by Tc1 has a limited distribution. Our data demonstrate that γ δ T cells, and, to a less extent, extrathymic α β T cells, mediate an immune response against B7+ EL-4 cells in allogeneic athymic mice.