Central role of thrombospondin-1 in the activation and clonal expansion ofinflammatory T cells

Thrombospondin-1 (TSP) is a transiently expressed matricellular protein kno wn to promote chemotaxis of leukocytes to inflammatory sites. However, TSP and its receptor CD36 are abundantly expressed in chronically inflamed tiss ues such as the rheumatoid synovium. Here, we show that TSP provides the co stimulatory signal that is necessary for the activation of autoreactive T c ells. Data presented reveal that TSP-mediated costimulation is achieved thr ough its independent interaction with CD36 on APCs and with CD47 on T cells . We propose that a CD47-TSP-CD36 trimolecular complex is a novel costimula tory pathway that significantly decreases the threshold of T cell activatio n. Consistent with the paradigm that lesions in rheumatoid synovitis are si tes of antigenic recognition, the characteristic focal expression of TSP on APCs such as macrophages and fibroblast-like synoviocytes suggest a centra l role of TSP in the expansion of tissue-infiltrating T cells.