Pathogenic T Cells in Celiac Disease Change Phenotype on Gluten Challenge: Implications for T-Cell-Directed Therapies.

Abstract

Gluten-specific CD4+ T cells being drivers of celiac disease (CeD) are obvious targets for immunotherapy. Little is known about how cell markers harnessed for T-cell-directed therapy can change with time and upon activation in CeD and other autoimmune conditions. In-depth characterization of gluten-specific CD4+ T cells and CeD-associated (CD38+ and CD103+ ) CD8+ and γδ+ T cells in blood of treated CeD patients undergoing a 3 day gluten challenge is reported. The phenotypic profile of gluten-specific cells changes profoundly with gluten exposure and the cells adopt the profile of gluten-specific cells in untreated disease (CD147+ , CD70+ , programmed cell death protein 1 (PD-1)+ , inducible T-cell costimulator (ICOS)+ , CD28+ , CD95+ , CD38+ , and CD161+ ), yet with some markers being unique for day 6 cells (C-X-C chemokine receptor type 6 (CXCR6), CD132, and CD147) and with integrin α4β7, C-C motif chemokine receptor 9 (CCR9), and CXCR3 being expressed stably at baseline and day 6. Among gluten-specific CD4+ T cells, 52% are CXCR5+ at baseline, perhaps indicative of germinal-center reactions, while on day 6 all are CXCR5- . Strikingly, the phenotypic profile of gluten-specific CD4+ T cells on day 6 largely overlaps with that of CeD-associated (CD38+ and CD103+ ) CD8+ and γδ+ T cells. The antigen-induced shift in phenotype of CD4+ T cells being shared with other disease-associated T cells is relevant for development of T-cell-directed therapies.

• Authors: Asbjørn Christophersen, Stephanie Zühlke, Eivind G Lund, Omri Snir, Shiva Dahal-Koirala, Louise Fremgaard Risnes, Jørgen Jahnsen, Knut E A Lundin, Ludvig M Sollid
• Journal: Advanced science (Weinheim, Baden-Wurttemberg, Germany) (Adv Sci (Weinh)) Vol. 8 Issue 21 Pg. e2102778 (11 2021) ISSN: 2198-3844 [Electronic] Germany
• PMID: 34495570 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Authors. Advanced Science published by Wiley-VCH GmbH.

Chemical References

• Antigens, CD
• HLA-DQ Antigens
• HLA-DQ2 antigen
• Integrin alpha Chains
• alpha E integrins
• Glutens
• ADP-ribosyl Cyclase 1

Topics

• ADP-ribosyl Cyclase 1 (metabolism)
• Antigens, CD (metabolism)
• CD4-Positive T-Lymphocytes (cytology, immunology, metabolism)
• CD8-Positive T-Lymphocytes (cytology, immunology, metabolism)
• Celiac Disease (immunology, therapy)
• Glutens (chemistry, immunology)
• HLA-DQ Antigens (chemistry, immunology)
• Humans
• Immunotherapy
• Integrin alpha Chains (metabolism)
• Intraepithelial Lymphocytes (cytology, immunology, metabolism)
• Phenotype
• Protein Multimerization