Human Follicular Dendritic Cells Inhibit Superantigen-Induced T-Cell Proliferation by Distinct Mechanisms

Abstract

Follicular dendritic cells (FDCs) reside within germinal centers of secondary lymphoid tissue where they play a critical role in antigen-driven immune responses. FDCs express numerous adhesion molecules that facilitate cellular interactions with B and T cells within the germinal center microenvironment. Although human FDCs have been shown to influence B-cell development, very little is known about the ability of FDCs to regulate T-cell responses. To investigate this functional aspect of FDCs, highly enriched preparations were isolated by magnetic cell separation using the FDC-restricted monoclonal antibody HJ2. We found that isolated human FDCs inhibited proliferation of both autologous and allogeneic T cells, and were dependent on the number of FDCs present. Inhibition by FDCs was observed using two serologically distinct superantigens at multiple concentrations (Staphylococcus enterotoxin A and B). In contrast, B cells failed to inhibit, and often augmented superantigen-induced T-cell proliferation. Antibody-blocking studies showed that CD54 and CD106 were involved in the ability of FDC to inhibit T-cell proliferative responses. When FDCs and T cells were separated by a semipermeable membrane, the inhibitory effect was partially abrogated, demonstrating that in addition to cell-cell interactions, a soluble factor(s) was also involved in the process. The addition of indomethicin to cultures improved the proliferative response in the presence of FDCs, indicating that inhibition was mediated, in part, by prostaglandins. These results indicate that FDCs regulate T-cell proliferation by two molecular mechanisms and that FDC:T-cell interactions may play a pivotal role in germinal center development.