IFN-γ and CD25 drive distinct pathologic features during hemophagocytic lymphohistiocytosis.

ABSTRACT:

Background

Inflammatory activation of CD8⁺ T cells can, when left unchecked, drive severe immunopathology. Hyperstimulation of CD8⁺ T cells through a broad set of triggering signals can precipitate hemophagocytic lymphohistiocytosis (HLH), a life-threatening systemic inflammatory disorder.

Objective

The mechanism linking CD8⁺ T-cell hyperactivation to pathology is controversial, with excessive production of IFN-γ and, more recently, excessive consumption of IL-2, which are proposed as competing hypotheses. We formally tested the proximal mechanistic events of each pathway in a mouse model of HLH.

Methods

In addition to reporting a complete autosomal recessive IFN-γ receptor 1-deficient patient with multiple aspects of HLH pathology, we

SUBMITTER: Humblet-Baron S 

PROVIDER: S-EPMC7117880 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature