Heparan sulfate modulate allogeneic T cell responses stimulated by dendritic cells
Heparan sulfate (HS) is a biologically active glycosaminoglycan which is released from cell surfaces or extracellular matrices under the circumstances of tissue injury or inflammation. We have reported previously that HS modulates T cell immune responses by direct activation of macrophages. Here, we examined the effect of free HS on dendritic cells (DC) as accessory cells in allogeneic mixed lymphocyte reactions. A T cell-enriched fraction of splenocytes from BALB/c mice was co-cultured with DC from C57BL/6 mice. DC were isolated from either spleen cells and cultured bone marrow cells with GM-CSF. Under suboptimal conditions (supplemented with 1% mouse serum), 103-104 DC treated with HS induced a greater allogeneic response than untreated DC. Counts per million at 4 days culture were as follows: splenic DC (103), 7751.3 +/- 1635.4 with HS vs. 1390.3 +/- 264.2 without, bone marrow DC (5×103), 6285.8 +/- 860.7 with HS vs. 1959.3 +/- 204.5 without. These results suggest that free HS may modulate cellular immune responses in the microenvironment of local inflammatory sites by providing inflammatory signals that modify the function of DC.
Kodaira, Y; Wrenshall, LE; Nair, S; Gilboa, E; Platt, JL
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