Soluble thrombospondin-1 suppresses T cell proliferation and enhances IL-10 secretion by antigen presenting cells stimulated with phytohemagglutinin

Thrombospondin-l (TSP-1) is different from other components of the extracel lular matrix (ECM) regarding its production and distribution. TSP-1 is cons idered to be released in large quantity in inflammatory sites and exogenous ly added TSP-I does not bind to preformed ECM but instead binds to cells. T o define the physiological role of TSP-1 in the immune system, we studied t he influence of TSP-1 on the in vitro culture of T cells and antigen-presen ting cells (APCs) in the presence of phytohemagglutinin. By adding soluble TSP-1 to the culture, T cell proliferation was suppressed and anti-inflamma tory cytokine IL-10 secretion by APCs was enhanced. The enhanced expression of IL-10 was also demonstrated at the mRNA level by RT-PCR using multi-pri mer kit for cytokines. The suppression of T cell proliferation and the enha ncement of IL-IO secretion with soluble TSP-I was inhibited by adding RGDS peptide or heparin. This result indicates that the effect of soluble TSP-1 may be caused by binding to its ligand(s) on T cells and/or APCs, resulting in transducing regulatory signals to the cells or disturbing appropriate i nteraction between T cells and APCs. We therefore propose that TSP-I is an immunosuppressive modulator which may play a role in inflammatory sites.