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Deficient resident memory T-cell and CD8 T-cell response to commensals in inflammatory bowel disease

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Title: Deficient resident memory T-cell and CD8 T-cell response to commensals in inflammatory bowel disease
Authors: Noble, A
Durant, L
Reddi, D
O'Connor, M
Hoyles, L
Segal, J
Man, R
Hendy, P
Bouri, S
Arebi, N
Akbar, A
Carding, S
Knight, S
Item Type: Journal Article
Abstract: Background and Aims The intestinal microbiota is closely associated with resident memory lymphocytes in mucosal tissue. We sought to understand how acquired cellular and humoral immunity to the microbiota differ in health versus inflammatory bowel disease [IBD]. Methods Resident memory T cells [Trm] in colonic biopsies and local antibody responses to intraepithelial microbes were analysed. Systemic antigen-specific immune T and B cell memory to a panel of commensal microbes was assessed. Results Systemically, healthy blood showed CD4 and occasional CD8 memory T cell responses to selected intestinal bacteria, but few memory B cell responses. In IBD, CD8 memory T cell responses decreased although B cell responses and circulating plasmablasts increased. Possibly secondary to loss of systemic CD8 T cell responses in IBD, dramatically reduced numbers of mucosal CD8+ Trm and γδ T cells were observed. IgA responses to intraepithelial bacteria were increased. Colonic Trm expressed CD39 and CD73 ectonucleotidases, characteristic of regulatory T cells. Cytokines/factors required for Trm differentiation were identified, and in vitro-generated Trm expressed regulatory T cell function via CD39. Cognate interaction between T cells and dendritic cells induced T-bet expression in dendritic cells, a key mechanism in regulating cell-mediated mucosal responses. Conclusions A previously unrecognised imbalance exists between cellular and humoral immunity to the microbiota in IBD, with loss of mucosal T cell-mediated barrier immunity and uncontrolled antibody responses. Regulatory function of Trm may explain their association with intestinal health. Promoting Trm and their interaction with dendritic cells, rather than immunosuppression, may reinforce tissue immunity, improve barrier function, and prevent B cell dysfunction in microbiota-associated disease and IBD aetiology.
Issue Date: Apr-2020
Date of Acceptance: 30-Sep-2019
URI: http://hdl.handle.net/10044/1/74319
DOI: 10.1093/ecco-jcc/jjz175
ISSN: 1873-9946
Publisher: Oxford University Press (OUP)
Start Page: 525
End Page: 537
Journal / Book Title: Journal of Crohn's and Colitis
Volume: 14
Issue: 4
Copyright Statement: © European Crohn’s and Colitis Organisation 2019. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: Dendritic cells
T lymphocytes
1103 Clinical Sciences
Gastroenterology & Hepatology
Publication Status: Published
Online Publication Date: 2019-11-22
Appears in Collections:Department of Metabolism, Digestion and Reproduction
Department of Surgery and Cancer
Department of Infectious Diseases
Faculty of Medicine
School of Public Health