The DOI matches its Crossref record; 42 of the 43 references it cites were found in a registry or an index.
CD4+ CD7- CD28- T cells are expanded in rheumatoid arthritis and are characterized by autoreactivity.
Open accessAbstract
Clonal expansion of CD4+ T cells is a characteristic finding in patients with RA and is only infrequently found in patients with psoriatic arthritis and healthy controls. Expanded CD4+ clonotypes are present in the blood, infiltrate into the joint, and persist over years. We have not addressed the question of whether the expanded clonotypes have unique functional and phenotypic properties which may explain the preferential in vivo expansion in RA. In contrast to most CD4+ T cells, expanded clonotypes lacked the expression of the CD28 and CD7 cell surface molecules. Accordingly, the subsets of CD4+ CD28- (9.7 vs 1.7, P = 0.00002) and CD4+ CD7- T cells (21.5 vs 12.26, P = 0.018) were increased in RA patients compared with age-matched normal individuals. Despite the lack of CD28 expression, clonally expanded CD4+ T cells were not anergic but proliferated in response to immobilized anti-CD3 and could be maintained in tissue culture. In vivo expanded CD4+ T cells were autoreactive to ubiquitously distributed autoantigens. They responded in an autologous mixed lymphocyte reaction, and T cell clones isolated from selected patients proliferated to autologous peripheral blood adherent cells. These data suggest that in RA patients selected CD4+ T cells which share the CD7- CD28- phenotype escape from peripheral tolerance.
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Self-citation
Metadata
- Authors
- Schmidt, D., Goronzy, J. J., & Weyand, C. M.
- Affiliations
- Mayo Clinic (US)
- Venue
- Journal of Clinical Investigation
- Published
- 1996-05-01
- Volume
- 97
- Issue
- 9
- Pages
- 2027-2037
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC507276
- OpenAlex
- W1982865105
- Cited by
- 482
- References
- 43
- Citations by year
- 2026: 3 · 2025: 11 · 2024: 10 · 2023: 5 · 2022: 13 · 2021: 15 · 2020: 12 · 2019: 15 · 2018: 10 · 2017: 18 · 2016: 7 · 2015: 20 · 2014: 12 · 2013: 23 · 2012: 11
- FWCI
- 18.26
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Arthritis Foundation
- Mayo Foundation for Medical Education and Research
- National Institutes of Health
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR041974, R01 AR 41974, R01AR042527, R01AR42527)
- Topics
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Keywords
- rheumatoid arthritis, CD4+ T cells, clonal expansion, CD28, CD7, autoreactivity, peripheral tolerance, T cell anergy, autoantigens, mixed lymphocyte reaction, T cell proliferation, psoriatic arthritis
- MeSH terms
- Arthritis, Rheumatoid, Autoantigens, Base Sequence, Clone Cells, Humans, Lymphocyte Activation, Molecular Sequence Data, CD4-Positive T-Lymphocytes, Immunophenotyping, T-Lymphocyte Subsets, CD28 Antigens, Antigens, CD7
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