ANTIGEN-SPECIFIC IMMUNE-RESPONSES IN CATTLE WITH INHERITED BETA(2)-INTEGRIN DEFICIENCY

The significance of beta(2)-integrins for the generation of antigen-sp ecific immune responses in vivo was studied employing the bovine model of beta(2)-integrin deficiency. To that end four cattle with bovine l eukocyte adhesion deficiency (BLAD) and healthy age-matched controls w ere immunized with tetanus toroid (TT) and rabies virus (RV) vaccines three times in monthly intervals. In addition, two animals with BLAD a nd three controls received a fourth vaccination 8 months after the sta rt of the study. Proliferative responses of peripheral blood mononucle ar cells (PBMC) to the antigens TT and RV as well as specific serum im munoglobulin G (IgG) titers were determined in intervals for up to 10 months after primary vaccination. Proliferative responses of PBMC to T T and RV were substantially lower in cattle with BLAD than in controls , although PBMC from cattle with BLAD were shown to have the capacity to proliferate in the response to the mitogen concanavalin A. Occurren ce of antigen-specific Ige titers was delayed and they were considerab ly lower in cattle with BLAD compared to controls. Finally, treatment of TT-and RV-stimulated PBMC from an immunized control with different concentrations of the anti-CD18 monoclonal antibody R15.7 resulted in a dose-dependent inhibition of lymphocyte proliferation to almost 100% . The results of the present study show that beta(2)-integrin deficien cy leads to delayed and severely impaired immune responsiveness in viv o. The observations that antibody production, although considerably de layed and impaired, does occur and that apparently class-switching tak es place in BLAD indicate T-cell reactivity in vivo. (C) 1997 Elsevier Science B.V.