Dysfunction of T cell receptor AV24AJ18+, BV11+ double-negative regulatory natural killer T cells in autoimmune diseases.
Abstract | OBJECTIVE: METHODS: Peripheral blood from patients with RA (n = 20), SLE (n = 18), SSc (n = 13), and SS (n = 17), as well as from healthy donors (n = 13) and patients with Behçet's disease (BD; n = 20), was examined by flow cytometry to determine the number of TCR AV24+,BV11+ DN T cells. PBLs from 10 RA, 10 SLE, 8 SSc, and 9 SS patients, as well as from 7 healthy subjects, were cultured in vitro with alpha-GalCer, and the number of TCR AV24+,BV11+ DN NKT cells was estimated. APCs from responder and nonresponder patients were cocultured with NKT cells from responder and nonresponder patients. RESULTS: The mean +/- SEM number of TCR AV24+,BV11+ DN NKT cells per ml of whole blood was found to be 48.8+/-10.0 in RA patients, 50.6+/-12.9 in SLE patients, 80.8+/-30.6 in SSc patients, and 40.0+/-11.7 in SS patients, while 290.0+/-69.6 and 321.2+/-103.4 NKT cells were present in healthy subjects and BD patients, respectively (P < 0.01). Three of 10 RA patients, 5 of 10 SLE patients, 4 of 8 SSc patients, and 6 of 9 SS patients (a total of 18 of 37 patients, or 48.6%) responded to alpha-GalCer, indicating that patients could be divided into two groups: alpha-GalCer responders and nonresponders. In contrast, NKT cells from all healthy subjects proliferated against alpha-GalCer. APCs from all nonresponder patients were found to function as alpha-GalCer-presenting cells, while NKT cells from nonresponders did not expand even in the presence of APCs from normal responders. CONCLUSION: These findings strongly suggest that patients with autoimmune diseases can be divided into two groups ( alpha-GalCer responders and nonresponders). They also suggest that the reduced numbers of NKT cells in patients with autoimmune diseases may be due to an inadequate amount of alpha-GalCer-like natural ligands (i.e., adequate in only 48.6% of patients) for the induction of NKT cells in vivo, or to a dysfunction in the NKT cells themselves (in 51.4% of patients).
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Authors | S Kojo, Y Adachi, H Keino, M Taniguchi, T Sumida |
Journal | Arthritis and rheumatism
(Arthritis Rheum)
Vol. 44
Issue 5
Pg. 1127-38
(May 2001)
ISSN: 0004-3591 [Print] United States |
PMID | 11352245
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Galactosylceramides
- RNA Splice Sites
- Receptors, Antigen, T-Cell, alpha-beta
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Topics |
- Antigen Presentation
(drug effects, immunology)
- Arthritis, Rheumatoid
(immunology, metabolism)
- Autoimmune Diseases
(immunology, metabolism)
- Behcet Syndrome
(immunology, metabolism)
- Cloning, Molecular
- Coculture Techniques
- Female
- Flow Cytometry
- Galactosylceramides
(pharmacology)
- Humans
- Killer Cells, Natural
(cytology, immunology, metabolism)
- Lupus Erythematosus, Systemic
(immunology, metabolism)
- Male
- Middle Aged
- RNA Splice Sites
(genetics)
- Receptors, Antigen, T-Cell, alpha-beta
(genetics, immunology, metabolism)
- Scleroderma, Systemic
(immunology, metabolism)
- Th2 Cells
(cytology, immunology, metabolism)
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