Circulating CD103+ γδ and CD8+ T cells are clonally shared with tissue-resident intraepithelial lymphocytes in celiac disease

• Published in: Mucosal immunology Vol. 14; no. 4; pp. 842 - 851
• Main Authors: Risnes, Louise F., Eggesbø, Linn M., Zühlke, Stephanie, Dahal-Koirala, Shiva, Neumann, Ralf S., Lundin, Knut E.A., Christophersen, Asbjørn, Sollid, Ludvig M.
• Format: Journal Article
• Language: English
• Published: New York Elsevier Inc 01.07.2021; Nature Publishing Group US; Elsevier Limited
• Subjects: Allergology; Antibodies; Antigens, CD - metabolism; Biomedical and Life Sciences; Biomedicine; Blood; CD103 antigen; CD38 antigen; CD4 antigen; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Celiac disease; Celiac Disease - etiology; Celiac Disease - metabolism; Celiac Disease - pathology; Clonal Evolution - genetics; Clonal Evolution - immunology; Gastroenterology; Gluten; Glutens - immunology; Humans; Immunohistochemistry; Immunology; Immunophenotyping; Integrin alpha Chains - metabolism; Intraepithelial Lymphocytes - immunology; Intraepithelial Lymphocytes - metabolism; Lymphocyte Count; Lymphocytes; Lymphocytes T; Receptors, Antigen, T-Cell, alpha-beta - immunology; Receptors, Antigen, T-Cell, gamma-delta - metabolism; T cell receptors; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism
• ISSN: 1933-0219; 1935-3456; 1935-3456
• DOI: 10.1038/s41385-021-00385-8

Gut intraepithelial γδ and CD8+ αβ T lymphocytes have been connected to celiac disease (CeD) pathogenesis. Based on the previous observation that activated (CD38+), gut-homing (CD103+) γδ and CD8+ αβ T cells increase in blood upon oral gluten challenge, we wanted to shed light on the pathogenic involvement of these T cells by examining the clonal relationship between cells of blood and gut during gluten exposure. Of 20 gluten-challenged CeD patients, 8 and 10 had increase in (CD38+CD103+) γδ and CD8+ αβ T cells, respectively, while 16 had increase in gluten-specific CD4+ T cells. We obtained γδ and αβ TCR sequences of >2500 single cells from blood and gut of 5 patients, before and during challenge. We observed extensive sharing between blood and gut γδ and CD8+ αβ T-cell clonotypes even prior to gluten challenge. In subjects with challenge-induced surge of γδ and/or CD8+ αβ T cells, as larger populations of cells analyzed, we observed more expanded clonotypes and clonal sharing, yet no discernible TCR similarities between expanded and/or shared clonotypes. Thus, CD4+ T cells appear to drive expansion of clonally diverse γδ or CD8+ αβ T-cell clonotypes that may not be specific for the gluten antigen.