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Inherited defects in lymphocyte cytotoxic activity
Author(s) -
Schmid Jana P.,
Côte Marjorie,
Ménager Mickaël M.,
Burgess Agathe,
Nehme Nadine,
Ménasché Gaël,
Fischer Alain,
De Saint Basile Geneviève
Publication year - 2010
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/j.0105-2896.2010.00890.x
Subject(s) - cytotoxic t cell , biology , immune system , immunology , effector , lymphocyte , in vitro , genetics
Summary: The granule‐dependent cytotoxic activity of lymphocytes plays a critical role in the defense against virally infected cells and tumor cells. The importance of this cytotoxic pathway in immune regulation is evidenced by the severe and often fatal condition, known as hemophagocytic lymphohistiocytic syndrome (HLH) that occurs in mice and humans with genetically determined impaired lymphocyte cytotoxic function. HLH manifests as the occurrence of uncontrolled activation of T lymphocytes and macrophages infiltrating multiple organs. In this review, we focus on recent advances in the characterization of effectors regulating the release of cytotoxic granules, and on the role of this cytotoxic pathway in lymphocyte homeostasis and immune surveillance. Analysis of the mechanisms leading to the occurrence of hemophagocytic syndrome designates γ‐interferon as an attractive therapeutic target to downregulate uncontrolled macrophage activation, which sustains clinical and biological features of HLH.