The regulatory potential of CD8+TCRgammadelta+NKG2A+ intraepithelial T-cells in Celiac
Kofi
what's seen in IBD.
J Clin Invest. 2008 Jan;118(1):281-93
Small intestinal CD8+TCRgammadelta+NKG2A+ intraepithelial lymphocytes
have attributes of regulatory cells in patients with celiac disease.
Bhagat G, Naiyer AJ, Shah JG, Harper J, Jabri B, Wang TC, Green PH,
Manavalan JS.
Department of Pathology, Columbia University College of Physicians and
Surgeons, New York, New York 10032, USA.
Intraepithelial lymphocytes (IELs) bearing the gammadelta TCR are more
abundant in the small intestinal mucosa of patients with celiac disease
(CD) compared with healthy individuals. However, their role in disease
pathogenesis is not well understood. Here, we investigated the
functional attributes of TCRgammadelta+ IELs isolated from intestinal
biopsies of patients with either active celiac disease (ACD) or those on
a gluten-free diet (GFD). We found that compared with individuals with
ACD, individuals on GFD have a higher frequency of CD8+TCRgammadelta+
IELs that express the inhibitory NK receptor NKG2A and intracellular
TGF-beta1. TCR triggering as well as cross-linking of NKG2A increased
both TGF-beta1 intracellular expression and secretion in vitro.
Coculture of sorted TCRgammadelta+NKG2A+ IELs, IL-15-stimulated
TCRalphabeta+ IELs, and HLA-E+ enterocytes resulted in a decreased
percentage of cytotoxic CD8+TCRalphabeta+ IELs expressing intracellular
IFN-gamma and granzyme-B and surface NKG2D. This inhibition was
partially abrogated by blocking either TGF-beta alone or both NKG2A and
HLA-E. Thus, our data indicate that suppression was at least partially
mediated by TGF-beta secretion as a result of engagement of NKG2A with
its ligand, HLA-E, on enterocytes and/or TCRalphabeta+ IELs. These
findings demonstrate that human small intestinal CD8+TCRgammadelta+ IELs
may have regulatory potential in celiac disease.
Publication Types:
* Research Support, Non-U.S. Gov't
PMID: 18064301