Mixed hematopoietic or T-cell chimerism above a minimal threshold restores perforin-dependent immune regulation in perforin-deficient mice.

ABSTRACT: Defects in perforin and related genes lead to a loss of normal immune regulation and underlie hemophagocytic lymphohistiocytosis (HLH), which requires hematopoietic cell transplantation for long-term cure. However, transplantation may be complicated by the development of mixed chimerism and uncertainty regarding the risk of HLH recurrence. To help clarify this risk and investigate how perforin influences immune activation, we studied perforin-mediated immune regulation in the context of mixed chimerism using a murine model of HLH. We found that there is a distinct threshold of ∼10% to 20% perforin expression with either mixed hematopoietic or CD8(+) T cell chimerism, above which immune regulation was reestablished. These findings demonstrate that perforin-mediated immunoregulation function

SUBMITTER: Terrell CE 

PROVIDER: S-EPMC3795460 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature