Thrombospondin-1 derived from APCs regulates their capacity for allosensitization.
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| Abstract |
Thrombospondin (TSP)-1 is a matricellular glycoprotein with immunoregulatory properties, which include inhibition of APC function. We show in transplantation that TSP-1 inhibits T cell allosensitization and consequently suppresses immune rejection. This was revealed by comparing wild-type (WT) versus TSP-1 null allografts in corneal transplantation, as the cornea is a rich source of TSP-1. Compared with only 50% of rejected WT allografts, nearly all TSP-1 null allografts succumbed to rejection. This effect was reflected by donor-derived APCs, which exhibited a distinctively greater capacity for allosensitization in transplanted hosts. Corroborated in MLRs, greater proliferation levels and robust IFN-γ (but not IL-10)-positive T cells resulted from stimulation by TSP-1 null APCs relative to WT ones. Moreover, enhanced expression of MHC class II and B7 maturation markers were detected on TSP-1 null APCs during inflammation. Increased expression of CCR7 was further matched by enhanced lymph node migration of TSP-1 null APCs posttransplantation. We therefore conclude that APC-derived TSP-1 suppresses their capacity to allosensitize T cells, and this regulation stems from their resistance to taking on a mature form. Future strategies targeting APCs for TSP-1 upregulation may thus be effective in promoting allograft survival.
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| Authors | Daniel R Saban, Felix Bock, Sunil K Chauhan, Sharmila Masli, Reza Dana |
| Journal | Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 185 Issue 8 Pg. 4691-7 (Oct 15 2010) ISSN: 1550-6606 [Electronic] United States |
| PMID | 20844200 (Publication Type: Journal Article, Research Support, N.I.H., Extramural) |
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