| First Author | Ying H | Year | 2012 |
| Journal | PLoS One | Volume | 7 |
| Issue | 3 | Pages | e32892 |
| PubMed ID | 22479345 | Mgi Jnum | J:224202 |
| Mgi Id | MGI:5661662 | Doi | 10.1371/journal.pone.0032892 |
| Citation | Ying H, et al. (2012) Genetic or pharmaceutical blockade of phosphoinositide 3-kinase p110delta prevents chronic rejection of heart allografts. PLoS One 7(3):e32892 |
| abstractText | Chronic rejection is the major cause of long-term heart allograft failure, characterized by tissue infiltration by recipient T cells with indirect allospecificity. Phosphoinositol-3-kinase p110delta is a key mediator of T cell receptor signaling, regulating both T cell activation and migration of primed T cells to non-lymphoid antigen-rich tissue. We investigated the effect of genetic or pharmacologic inactivation of PI3K p110delta on the development of chronic allograft rejection in a murine model in which HY-mismatched male hearts were transplanted into female recipients. We show that suppression of p110delta activity significantly attenuates the development of chronic rejection of heart grafts in the absence of any additional immunosuppressive treatment by impairing the localization of antigen-specific T cells to the grafts, while not inducing specific T cell tolerance. p110delta pharmacologic inactivation is effective when initiated after transplantation. Targeting p110delta activity might be a viable strategy for the treatment of heart chronic rejection in humans. |
