B7 costimulation is critical for antibody class switching and CD8(+) cytotoxic T-lymphocyte generation in the host response to vesicular stomatitis virus

Antibody and cytotoxic T-lymphocyte (CTL) responses have critical roles in eliminating many viral infections. In addition to stimulation of the T-cell receptor, T cells require costimulatory signals to respond optimally. We e valuated the role of B7 costimulatory molecules (B7-1 and B7-2) in the immu ne response to viral infection using vesicular stomatitis virus (VSV) and m ice lacking either B7-1 or B7-2 or both molecules. Mice lacking both B7-1 a nd B7-2 had essentially no anti-VSV immunoglobulin G1 (IgG1) response, decr eased IgG2a responses, and normal IgM responses, while mice lacking either B7-1 or B7-2 had unaltered anti-VSV antibody responses compared to wild-typ e mice. Depletion of CD4(+) cells further reduced the IgG2a response in mic e lacking both B7 molecules, suggesting that CD4(-) cells may supply help f or IgG2a in the absence of B7 costimulation. The absence of both B7 molecul es profoundly reduced generation of both primary and secondary VSV-specific class I major histocompatibility complex (MHC)-restricted CTL, whereas VSV -specific CTL responses in mice lacking either B7-1 or B7-2 were similar to those of wild-type animals. Class I MHC-restricted CTL in wild-type mice w ere not dependent on CD4(+) cells, suggesting that the failure of CTL in th e absence of B7s is due to a lack of B7 costimulation directly to the CD8() CTL. These data demonstrate that B7-1 and B7-2 have critical, overlapping functions in the antibody and CTL responses to this viral infection.