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Rheumatoid Arthritis
CD4+,CD28− T cells in rheumatoid arthritis patients combine features of the innate and adaptive immune systems
Article first published online: 25 JAN 2001
DOI: 10.1002/1529-0131(200101)44:1<13::AID-ANR3>3.0.CO;2-6
Copyright © 2001 by the American College of Rheumatology
1529-0131/asset/cover.gif?v=1&s=104d5c2bb8ef72deba26790b855af7ab80697a0e "Arthritis & Rheumatism")
Additional Information
How to Cite
Warrington, K. J., Takemura, S., Goronzy, J. J. and Weyand, C. M. (2001), CD4+,CD28− T cells in rheumatoid arthritis patients combine features of the innate and adaptive immune systems. Arthritis & Rheumatism, 44: 13–20. doi: 10.1002/1529-0131(200101)44:1<13::AID-ANR3>3.0.CO;2-6
Publication History
- Issue published online: 25 JAN 2001
- Article first published online: 25 JAN 2001
- Manuscript Accepted: 6 SEP 2000
- Manuscript Received: 2 MAY 2000
Funded by
- Mayo Foundation
- NIH. Grant Number: R01-AR-41974 and R01-AR-42527
- General Mills Foundation
- Abstract
- Article
- References
- Cited By
Abstract
Objective
To determine whether CD4+,CD28− T cells, which are expanded in patients with rheumatoid arthritis (RA), express receptors that typically regulate the function of natural killer (NK) cells.
Methods
Expression of the NK cell surface molecules CD158, p70, CD94, CD161, and CD8α on T cell subsets was determined by multicolor flow cytometric analysis of peripheral blood mononuclear cells from 36 RA patients. Expression of CD161 on tissue-infiltrating CD4 T cells was determined by 2-color immunohistochemistry analysis of synovial tissue samples.
Results
Killer cell–inhibitory receptors (KIR) and killer cell–activating receptors (KAR) were exclusively expressed on CD4+,CD28− T cells, with the CD158b molecule being the most frequently detected isoform. A coordinated mechanism inducing KIR/KAR expression was suggested by similarities in the expression of CD158b on CD4 and CD8 T cells. CD4+,CD28− T cells were also positive for CD8-αα homodimers, another characteristic shared with NK cells. Of the C-type lectin NK cell receptors (NK receptors), CD94 was consistently absent, but CD161 was found on a CD4 T cell population that is significantly expanded in RA patients (P = 0.01). Involvement in disease of NK receptor–expressing CD4 T cells was suggested by the presence of CD4+,CD161+ T cells in follicular microstructures typical of rheumatoid synovitis.
Conclusion
Patients with RA have an expanded and unusual subset of CD4 T cells that infiltrates the tissue lesions and is characterized by a deficiency of CD28, the expression of CD8-αα homodimers, and the expression of several types of HLA class I–recognizing NK receptors. CD4 T cells bearing NK receptors can bridge functions of the innate and adaptive immune systems, such as responsiveness to specific antigen, rapid release of interferon-γ, cytotoxicity, independence from classic costimulatory pathways, and integration of multiple activating and inhibitory signals to control effector functions.