Immunomodulation of Selective Naive T Cell Functions by p110? Inactivation Improves the Outcome of Mismatched Cell Transplantation.

ABSTRACT: Allogeneic hematopoietic stem cell transplantation (HSCT) can treat certain hematologic malignancies due to the graft versus leukemia (GvL) effect but is complicated by graft versus host disease (GvHD). Expression of the p110? catalytic subunit of the phosphoinositide 3-kinase pathway is restricted to leukocytes, where it regulates proliferation, migration, and cytokine production. Here, in a mouse model of fully mismatched hematopoietic cell transplantation (HCT), we show that genetic inactivation of p110? in T cells leads to milder GvHD, whereas GvL is preserved. Inactivation of p110? in human lymphocytes reduced T cell allorecognition. We demonstrate that both allostimulation and granzyme B expression were dependent on p110? in naive T cells, which are the main mediators of GvHD, whereas memory T cells were unaffected. Strikingly, p110? is not mandatory for either naive or memory T cells to mediate GvL. Therefore, immunomodulation of selective naive T cell functions by p110? inactivation improves the outcome of allogeneic HSCT.

SUBMITTER: Doisne JM 

PROVIDER: S-EPMC4542309 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature