title: Lymphocyte function during hepatic ischemia/reperfusion injury.
abstract: The liver is the primary organ affected by ischemia/reperfusion (I/R) injury after shock, surgical resection, or transplantation. The actions of myeloid leukocytes have been well studied and are thought to be the primary cells responsible for propagating the injury response. However, there is an emerging view that T lymphocytes can also regulate liver I/R-induced inflammation. Resident lymphocytes found within the liver include conventional alphabeta TCR cells as well as unconventional NK and gammadelta T cells. These lymphocytes can alter inflammation through the secretion of soluble mediators such as cytokines and chemokines or through cognate interactions in an antigen-dependent manner. Expression of these mediators will then result in the recruitment of more lymphocytes and neutrophils. There is evidence to suggest that T cell activation in the liver during I/R can be driven by antigenic or nonantigenic mechanisms. Finally, immune cells are exposed to different oxygen tensions, including hypoxia, as they migrate and function within tissues. The hypoxic environment during liver ischemia likely modulates T cell function, at least in part through the actions of hypoxia-inducible factor-1alpha. Further, this hypoxic environment leads to the increased concentration of extracellular adenosine, which is generally known to suppress T cell proinflammatory function. Altogether, the elucidation of T lymphocyte actions during liver I/R will likely allow for novel targets for therapeutic intervention.
authors.affiliation: The Laboratory of Trauma, Sepsis and Inflammation Research, Department of Surgery, University of Cincinnati, Cincinnati, Ohio, USA.
authors.forename: Charles C
authors.initials: CC
authors.lastname: Caldwell
authors.forename: Johannes
authors.initials: J
authors.lastname: Tschoep
authors.forename: Alex B
authors.initials: AB
authors.lastname: Lentsch
mesh_terms: D000818:Animals; D006801:Humans; D007249:Inflammation / Q000276:immunology; D008107:Liver Diseases / Q000276:immunology*; D015427:Reperfusion Injury / Q000276:immunology*; D013601:T-Lymphocytes / Q000502:physiology*