Genetic Deficiency of Interferon-γ Reveals Interferon-γ-Independent Manifestations of Murine Hemophagocytic Lymphohistiocytosis.

ABSTRACT:

Objective

Familial hemophagocytic lymphohistiocytosis (FHLH) is a complex cytokine storm syndrome caused by genetic abnormalities rendering CD8+ T cells and natural killer cells incapable of cytolytic killing. In murine models of FHLH, interferon-γ (IFNγ) produced by CD8+ T cells has been identified as a critical mediator of disease, and an IFNγ-blocking antibody (emapalumab) has recently been approved by the Food and Drug Administration. However, development of hemophagocytic lymphohistiocytosis (HLH)/macrophage activation syndrome (MAS) in patients who are genetically unresponsive to IFNγ questions the absolute necessity of IFNγ in driving disease. This study was undertaken to determine the necessity of IFNγ in driving HLH.

Methods

IFNγ^-/- Prf1^-/- mic

SUBMITTER: Burn TN 

PROVIDER: S-EPMC6994338 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature