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Human CD8 + intraepithelial lymphocytes: a unique model to study the regulation of effector cytotoxic T lymphocytes in tissue
Author(s) -
Jabri Bana,
Ebert Ellen
Publication year - 2007
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.1600-065x.2006.00481.x
Subject(s) - biology , intraepithelial lymphocyte , cytotoxic t cell , cd8 , t cell receptor , major histocompatibility complex , immunology , microbiology and biotechnology , population , t cell , mhc class i , ctl* , immune system , medicine , genetics , environmental health , in vitro
Summary: The epithelium of the human small intestine contains a large population of intraepithelial cytolytic αβ T‐cell receptor (TCR) CD8αβ T lymphocytes (IE‐CTLs), whose main role is to sustain epithelial integrity by rapidly eliminating infected and damaged cells. In mouse, the recognition of inducible/modified self‐molecules, i.e. non‐classical major histocompatibility complex (MHC) class I molecules, is mediated by the TCR and natural killer receptors (NKRs) co‐expressed on the cell surface of a non‐conventional autoreactive CD8αααβTCR cell subset. In contrast, in humans, the recognition of non‐classical MHC class I molecules induced by stress and inflammation on intestinal epithelial cells (IECs) is principally mediated by NKRs expressed on conventional CD8αβαβTCR cells. By sensing microenvironmental signals of inflammation and stress through NKRs, IE‐CTLs fine tune their TCR activation threshold. Furthermore, IE‐CTLs under particular conditions, involving interleukin‐15 upregulation, acquire the capacity to kill distressed intestinal epithelial cells in an antigen non‐specific manner. Adaptive IE‐CTLs appear hence to have autoreactive properties and modulate their immune response based on innate signals, reflecting the fitness of the tissue.