T-cell gene therapy for perforin deficiency corrects cytotoxicity defects and prevents hemophagocytic lymphohistiocytosis manifestations.

ABSTRACT:

Background

Mutations in the perforin 1 (PRF1) gene account for up to 58% of familial hemophagocytic lymphohistiocytosis syndromes. The resulting defects in effector cell cytotoxicity lead to hypercytokinemia and hyperactivation with inflammation in various organs.

Objective

We sought to determine whether autologous gene-corrected T cells can restore cytotoxic function, reduce disease activity, and prevent hemophagocytic lymphohistiocytosis (HLH) symptoms in in vivo models.

Methods

We developed a gammaretroviral vector to transduce murine CD8 T cells in the Prf^-/- mouse model. To verify functional correction of Prf^-/- CD8 T cells in vivo, we used a lymphocytic choriomeningitis virus (LCMV) epitope-transfected murine lung carcinoma cell tumor model

SUBMITTER: Ghosh S 

PROVIDER: S-EPMC6127027 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature