International Immunology Advance Access published online on March 28, 2006
International Immunology, doi:10.1093/intimm/dxl006
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1 Schepens Eye Research Institute, 20 Staniford Street, Boston, MA 02114, USA; Department of Ophthalmology, Harvard Medical School, 20 Staniford Street, Boston, MA 02114, USA
* To whom correspondence should be addressed. Eye-derived antigen-presenting cells (APCs) are known to contribute to the immune privilege status of the eye by inducing a form of peripheral tolerance that deviates Th1 type of pro-inflammatory immune responses. Similar systemic tolerance can also be induced by non-ocular APCs exposed to transforming growth factor *Deceased, March 15, 2004.
Received March 4, 2005
Accepted February 5, 2006
Article
Thrombospondin orchestrates the tolerance-promoting properties of TGF
Sharmila Masli 1 *,
Bruce Turpie 2,
and
J. Wayne Streilein 1 *
-treated antigen-presenting cells
2 Schepens Eye Research Institute, 20 Staniford Street, Boston, MA 02114, USA
Sharmila Masli, E-mail: smasli{at}vision.eri.harvard.edu
Abstract 
(TGF) in vitro. Such APCs were found to express enhanced levels of thrombospondin (TSP)-1, an extracellular matrix (ECM) protein. In this report, we analyzed the significance of TSP-1 in conferring tolerance-inducing properties on APCs. While TSP-treated APCs matched TGF-treated APCs in their functional ability to induce systemic tolerance, a deficiency of TSP-1 or its receptor CD36 prevented APCs from becoming tolerogenic in response to TGF. Exogenous TSP-1 restored tolerogenic ability of TGF-treated TSP-1 null APCs. Both TGF-treated TSP-1 null and CD36 knockout APCs failed to inhibit IL-12 secretion. Furthermore, TGF-treated TSP-1 null APCs, unlike similarly treated wild-type APCs, failed to increase secretion of active TGF. Similar to TGF, TSP could also up-regulate expression of MIP-2, TGF2 and tumor necrosis factor 
--all of which are required for tolerance induced by TGF-treated APCs. We conclude that TSP-1, an ECM protein induced by TGF treatment, orchestrates the changes in APC functional programs that equip these cells to promote tolerance of the eye-derived type.
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