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Citations to this article

Small intestinal CD8+TCRγδ+NKG2A+ intraepithelial lymphocytes have attributes of regulatory cells in patients with celiac disease
Govind Bhagat, … , Peter H.R. Green, John S. Manavalan
Govind Bhagat, … , Peter H.R. Green, John S. Manavalan
Published December 6, 2007
Citation Information: J Clin Invest. 2008;118(1):281-293. https://doi.org/10.1172/JCI30989.
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Research Article Immunology Article has an altmetric score of 3

Small intestinal CD8+TCRγδ+NKG2A+ intraepithelial lymphocytes have attributes of regulatory cells in patients with celiac disease

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Abstract

Intraepithelial lymphocytes (IELs) bearing the γδ 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 TCRγδ+ 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+TCRγδ+ IELs that express the inhibitory NK receptor NKG2A and intracellular TGF-β1. TCR triggering as well as cross-linking of NKG2A increased both TGF-β1 intracellular expression and secretion in vitro. Coculture of sorted TCRγδ+NKG2A+ IELs, IL-15–stimulated TCRαβ+ IELs, and HLA-E+ enterocytes resulted in a decreased percentage of cytotoxic CD8+TCRαβ+ IELs expressing intracellular IFN-γ and granzyme-B and surface NKG2D. This inhibition was partially abrogated by blocking either TGF-β alone or both NKG2A and HLA-E. Thus, our data indicate that suppression was at least partially mediated by TGF-β secretion as a result of engagement of NKG2A with its ligand, HLA-E, on enterocytes and/or TCRαβ+ IELs. These findings demonstrate that human small intestinal CD8+TCRγδ+ IELs may have regulatory potential in celiac disease.

Authors

Govind Bhagat, Afzal J. Naiyer, Jayesh G. Shah, Jason Harper, Bana Jabri, Timothy C. Wang, Peter H.R. Green, John S. Manavalan

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2015 2014 2013 2012 2011 2010 2009 2008 Total
Citations: 3 3 7 5 10 8 4 5 3 5 7 6 6 6 1 6 2 87
Citation information
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Citations to this article in year 2012 (6)

Title and authors Publication Year
The Role of the Intestinal Context in the Generation of Tolerance and Inflammation
BS Reis, D Mucida
Clinical and Developmental Immunology 2012
Intraepithelial γδ T Cells Remain Increased in the Duodenum of AIDS Patients Despite Antiretroviral Treatment
DE Nilssen, P Brandtzaeg
PloS one 2012
Decrease of Peripheral and Intestinal NKG2A-Positive T Cells in Patients with Ulcerative Colitis
T Katsurada, W Kobayashi, U Tomaru, T Baba, S Furukawa, A Ishizu, K Takeda, N Sakamoto, M Asaka, H Takeda, M Kasahara
PloS one 2012
Intraepithelial lymphocytes in celiac disease immunopathology
V Abadie, V Discepolo, B Jabri
Seminars in Immunopathology 2012
Defining the nature of human γδ T cells: a biographical sketch of the highly empathetic
S Kalyan, D Kabelitz
Cellular and Molecular Immunology 2012
Tumor-Infiltrating    T Lymphocytes Predict Clinical Outcome in Human Breast Cancer
C Ma, Q Zhang, J Ye, F Wang, Y Zhang, E Wevers, T Schwartz, P Hunborg, MA Varvares, DF Hoft, EC Hsueh, G Peng
Journal of immunology (Baltimore, Md. : 1950) 2012

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