Reprogramming of CTLs into natural killer-like cells in celiac disease. - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of Experimental Medicine Année : 2006

Reprogramming of CTLs into natural killer-like cells in celiac disease.

Résumé

Celiac disease is an intestinal inflammatory disorder induced by dietary gluten in genetically susceptible individuals. The mechanisms underlying the massive expansion of interferon gamma-producing intraepithelial cytotoxic T lymphocytes (CTLs) and the destruction of the epithelial cells lining the small intestine of celiac patients have remained elusive. We report massive oligoclonal expansions of intraepithelial CTLs that exhibit a profound genetic reprogramming of natural killer (NK) functions. These CTLs aberrantly expressed cytolytic NK lineage receptors, such as NKG2C, NKp44, and NKp46, which associate with adaptor molecules bearing immunoreceptor tyrosine-based activation motifs and induce ZAP-70 phosphorylation, cytokine secretion, and proliferation independently of T cell receptor signaling. This NK transformation of CTLs may underlie both the self-perpetuating, gluten-independent tissue damage and the uncontrolled CTL expansion leading to malignant lymphomas in severe forms of celiac disease. Because similar changes were detected in a subset of CTLs from cytomegalovirus-seropositive patients, we suggest that a stepwise transformation of CTLs into NK-like cells may underlie immunopathology in various chronic infectious and inflammatory diseases.

Dates et versions

hal-00166286 , version 1 (02-08-2007)

Identifiants

Citer

Bertrand Meresse, Shane A Curran, Cezary Ciszewski, Gerasim Orbelyan, Mala Setty, et al.. Reprogramming of CTLs into natural killer-like cells in celiac disease.. Journal of Experimental Medicine, 2006, 203 (5), pp.1343-55. ⟨10.1084/jem.20060028⟩. ⟨hal-00166286⟩
60 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Mastodon Facebook X LinkedIn More