Fibroblasts rescure butyric acid-induced T-cell apoptosis; role of adhesion molecules

Objectives: We previously demonstrated that cellular mechanisms involved in butyric acid-induce T-cell apoptosis (J. Immunol., 2003, 171). We also reported that human gingival fibroblasts rescue butyric acid-induced T-cell apoptosis via the proinflammatory cytokines such as IL-6 and IL-11, which were produced in fibroblasts stimulated with butyric acid (Infect. Immun., 2002, 70). In this study, we assessed whether the T cell adhesion to human gingival fibroblasts (Gin 1 cells) regulates the susceptibility of T cells to butyric acid-induced apoptosis. Methods: Number of Jurkat cells adhered to Gin-1 was detected with conforcal laser scanning microscope. Expression of adhesion molecules was examined by PCR. Monoclonal antibodies against adhesion molecules were employed in this study. Results: The number of Jurkat cells adhered to gingival fibroblasts was significantly increased by addition of butyric acid. All Jurkat cells adhered to Gin-1 cells were live cells in contrast to non-adhered cells drop into apoptosis. The increase in T cell adhesion to fibroblasts was also observed when Jurkat cells but not Gin 1 cells were pretreated with butyric acid. CD44, very late antigen (VLA-2) and VLA-5 but not leukocyte function-associated antigen 1 (LFA-1) and VLA-4 expressions on Jurkat cells were increased by butyric acid-treatment. Furthermore, pretreatment of butyric acid-sensitized Jurkat cells with monoclonal antibodies against CD44, VLA-2 and VLA-5 but not LFA-1 and VLA-4 followed by co-culture with Gin-1 cells attenuated T-cell adhesion to fibroblasts. Conclusions: These results demonstrated that the T-cell adherence to fibroblasts is facilitated by butyric acid, and that butyric acid-induced T-cell apoptosis is down-regulated by the adhesion to gingival fibroblasts through the interaction with the adhesion molecule such as CD44, VLA-2 and VLA-5, expressed on T cells stimulated with butyric acid. This work was supported by a Grant-in-aid (13671965) from the ministry of Education, Science, Sports and Culture of Japan.