%0 Journal Article
%T Genetic or Pharmaceutical Blockade of Phosphoinositide 3-Kinase P110¦Ä Prevents Chronic Rejection of Heart Allografts
%A Huijun Ying
%A Hongmei Fu
%A Marlene L. Rose
%A Ann M. McCormack
%A Padmini Sarathchandra
%A Klaus Okkenhaug
%A Federica M. Marelli-Berg
%J PLOS ONE
%D 2012
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0032892
%X 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 p110¦Ä 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 p110¦Ä 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 p110¦Ä 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. p110¦Ä pharmacologic inactivation is effective when initiated after transplantation. Targeting p110¦Ä activity might be a viable strategy for the treatment of heart chronic rejection in humans.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0032892