HIV‐specific T lymphocyte immunity in mice immunized with a recombinant vaccinia virus

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Abstract
Infection by the human immunodeficiency virus (HIV) induces T cell immunity in humans, chimpanzees and macaques. The protective value of this immune response is not clear. We have consequently developed a murine experimental system to study HIV‐specific CD4 and CD8 T lymphocyte immunity in vitro and in vivo. BALB/c, DBA/2 and C3H/He mice were immunized with vaccinia virus (VV) recombinant VV‐11.39 which expresses the gp160 glycoprotein of HIV‐1. Primary and secondary cytotoxic T lymphocyte response to HIV were detected with histocompatible mouse target cells transfected with the HIV‐1 env gene. Killer cells were positive for the Thy‐1 and Ly‐2 (CD8) T cell markers, and were restricted by class IH‐2 histocompatibility antigens. Immunological memory specific for HIV‐1 envelope antigens was clearly induced by vaccination with W‐11.39: spleen cells from mice vaccinated 4 weeks or more prior to assay generated CD4 and CD8 T lymphocyte responses following stimulation in vitro with HIV envelope antigens. The intensity of these responses increased with consecutive vaccinations, indicating that HIV‐specific precursor T cell pools were progressively amplified. Finally, DBA/2 mice vaccinated with VV‐11.39 developed protective immunity against a syngeneic tumor which expresses HIV‐1 env antigens, leading to accelerated tumor rejection and increased survival.