Blood, Vol. 94 No. 1 (July 1), 1999:
pp. 216-224
Human Follicular Dendritic Cells Inhibit Superantigen-Induced T-Cell
Proliferation by Distinct Mechanisms
Anthony W. Butch,
Kathleen A. Kelly,
Michael S. Willbanks, and
Xinwen Yu
From the Departments of Pathology, Microbiology, and Immunology,
University of Arkansas for Medical Sciences, Little Rock, AR.
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.
