| First Author | Saban DR | Year | 2010 |
| Journal | J Immunol | Volume | 185 |
| Issue | 8 | Pages | 4691-7 |
| PubMed ID | 20844200 | Mgi Jnum | J:164736 |
| Mgi Id | MGI:4835100 | Doi | 10.4049/jimmunol.1001133 |
| Citation | Saban DR, et al. (2010) Thrombospondin-1 derived from APCs regulates their capacity for allosensitization. J Immunol 185(8):4691-7 |
| abstractText | 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-gamma (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. |
