| Two of the most important costimulatory molecules for T cell activation are provided by the B7 family members B7-1(CD80) and B7-2(CD86). Both molecules bind to CD28 and CTLA-4, providing positive and negative signals respectively. In order to define biologic differences intrinsic to the B7-1 and B7-2 molecules themselves, double recombinant Vaccinia virus vectors were constructed which express antigens targeted to three distinct cellular compartments together with B7-1 and B7-2. Analysis of antigen-specific responses after immunization of mice with these vectors indicated that B7-2 selectively promotes cytotoxic T lymphocyte (CTL) generation for antigens expressed in all three compartments. Conversely, B7-1 selectively promotes humoral immunity. These results reveal distinct immunologic functions intrinsic to B7-1 and B7-2.; However, despite the potent abilities of B7-1 and B7-2 to affect antigen-specific immune responses, attempts to augment tumor specific immune responses capable of protecting against tumor growth in vivo by vaccinating naïve mice with these vectors failed to result in increased tumor protection. In these experiments, improved CTL activity did not correspond with improved protection from tumor challenge which suggests that protective immunity may be mediated by more non-traditional effector mechanisms such as NK cell lysis, eosinophil activity, and macrophage secreted i-NOS toxicity. |
