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Published 29 April 2002. doi:10.1083/jcb.200109098
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© The Rockefeller University Press, 0021-9525/2002/4/509 $5.00
The Journal of Cell Biology, Volume 157, Number 3, April 29, 2002 509-519

Article

 Interactions of thrombospondins with {alpha}4ß1 integrin and CD47 differentially modulate T cell behavior

Zhuqing Li1, Maria J. Calzada1, John M. Sipes1, Jo Anne Cashel1, Henry C. Krutzsch1, Douglas S. Annis2, Deane F. Mosher2 and David D. Roberts1

1 Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892
2 Department of Medicine, University of Wisconsin-Madison, Madison, WI 53706

Address correspondence to David D. Roberts, National Institutes of Health, Building 10, Room 2A33, 10 Center Dr. MSC 1500, Bethesda, MD 20892-1500. Tel.: (301) 496-6264. Fax: (301) 402-0043. E-mail: droberts{at}helix.nih.gov

Thrombospondin (TSP)-1 has been reported to modulate T cell behavior both positively and negatively. We found that these opposing responses arise from interactions of TSP1 with two different T cell receptors. The integrin {alpha}4ß1 recognizes an LDVP sequence in the NH2-terminal domain of TSP1 and was required for stimulation of T cell adhesion, chemotaxis, and matrix metalloproteinase gene expression by TSP1. Recognition of TSP1 by T cells depended on the activation state of {alpha}4ß1 integrin, and TSP1 inhibited interaction of activated {alpha}4ß1 integrin on T cells with its counter receptor vascular cell adhesion molecule-1. The {alpha}4ß1 integrin recognition site is conserved in TSP2. A recombinant piece of TSP2 containing this sequence replicated the {alpha}4ß1 integrin–dependent activities of TSP1. The ß1 integrin recognition sites in TSP1, however, were neither necessary nor sufficient for inhibition of T cell proliferation and T cell antigen receptor signaling by TSP1. A second TSP1 receptor, CD47, was not required for some stimulatory responses to TSP1 but played a significant role in its T cell antigen receptor antagonist and antiproliferative activities. Modulating the relative expression or function of these two TSP receptors could therefore alter the direction or magnitude of T cell responses to TSPs.

Key Words: thrombospondins; integrins; chemotaxis; T cell antigen receptor; matrix metalloproteinases


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