Regulation of T cell alloimmunity by PI3Kγ and PI3Kδ

摘要: Phosphatidylinositol-3-kinases (PI3K) γ and δ are preferentially enriched in leukocytes, defects these signaling pathways have been shown to impair T cell activation. The effects of PI3Kγ PI3Kδ on alloimmunity remain underexplored. Here, we show that both -/- D910A/D910A mice receiving heart allografts suppression alloreactive effector cells delayed acute rejection. However, mutation also dampens regulatory (Treg). After treatment with low dose CTLA4-Ig, , but not PI3Κδ recipients exhibit indefinite prolongation allograft survival. Tregs increased apoptosis impaired Selective inhibition (using dual PI3Kγδ chemical inhibitors) shows compensates for the negative effect long-term These data serve as a basis future PI3K-based immune therapies transplantation.Phosphatidylinositol-3-kinases key regulators signaling. Here author show, using mouse transplantation models, or deficiency prolongs graft survival, selective reveals alternative transplant survival outcomes post CTLA4-Ig treatment.