Distinct phenotype of CD4+ T cells driving celiac disease identified in multiple autoimmune conditions
Open accessAbstract
Combining HLA-DQ-gluten tetramers with mass cytometry and RNA sequencing analysis, we find that gluten-specific CD4+ T cells in the blood and intestines of patients with celiac disease display a surprisingly rare phenotype. Cells with this phenotype are also elevated in patients with systemic sclerosis and systemic lupus erythematosus, suggesting a way to characterize CD4+ T cells specific for disease-driving antigens in multiple autoimmune conditions.
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In vitro expanded AQP4-specific T cells represent Tph-like rather than Tfh-like features.
“Thus, in vitro expanded AQP4-specific T cells represent Tph-like rather than Tfh-like features, as identified in AID patients before. 16,17,54”
From Autoantigen-specific CD4+ T cells acquire an exhausted phenotype and persist in human antigen-specific autoimmune diseases (2024) · cites this paper as [17]
The paper’s Abstract (page unavailable) reports that gluten-specific T cells lack a classical follicular T-helper phenotype and describes a similar CXCR5− phenotype in rheumatoid arthritis. It does not establish that in vitro-expanded AQP4-specific T cells have those features; its in vitro findings concern gluten-specific cells. (LLM, conf=0.83)
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- Authors
- Christophersen, A., Lund, E. G., Snir, O., Solà, E., Kanduri, C., Dahal-Koirala, S., Zühlke, S., Molberg, Ø., Utz, P. J., Rohani-Pichavant, M., Simard, J. F., Dekker, C. L., Lundin, K. E. A., Sollid, L. M., & Davis, M. M.
- Affiliations
- University of Oslo (NO)
- Hospital Clínic de Barcelona (ES)
- Oslo University Hospital (NO)
- Stanford University (US)
- Stanford Medicine (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Sollid, Ludvig M.
- Davis, Mark M.
- ORCID
- Venue
- Nature Medicine
- Published
- 2019-03-25
- Volume
- 25
- Issue
- 5
- Pages
- 734-737
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC6647859
- OpenAlex
- W2923342978
- Cited by
- 164
- References
- 34
- Citations by year
- 2026: 10 · 2025: 16 · 2024: 30 · 2023: 15 · 2022: 26 · 2021: 32 · 2020: 21 · 2019: 14
- FWCI
- 21.37
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- NORA - Norwegian Open Research Archives (submittedVersion, other-oa)
- Funders
- National Institutes of Health (UL1TR001085, UL1TR003142)
- National Institute of Allergy and Infectious Diseases (U19AI110491, R01AI125197, U19AI057229)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Gastroenterology › Celiac Disease Research and Management
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Keywords
- celiac disease, CD4+ T cells, systemic sclerosis, systemic lupus erythematosus, autoimmune disease, T cell phenotype, intestinal T cells
- MeSH terms
- Autoimmune Diseases, Celiac Disease, Glutens, HLA-DQ Antigens, Humans, Intestines, Lupus Erythematosus, Systemic, Scleroderma, Systemic, CD4-Positive T-Lymphocytes, Immunophenotyping, T-Lymphocyte Subsets
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