Dysfunction of T cell receptor AV24AJ18+,BV11+ double-negative regulatory natural killer T cells in autoimmune diseases

Satoshi Kojo, Yoshihiro Adachi, Hiroshi Keino, Masaru Taniguchi, Takayuki Sumida

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175 Citations (Scopus)

Abstract

Objective: We examined the reduction of T cell receptor (TCR) AV24+,BV11+ CD4-,CD8- (double-negative [DN]) natural killer T (NKT) cells in peripheral blood lymphocytes (PBLs) from patients with rheumatoid arthritis (RA), Systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and Sjögren's syndrome (SS) to analyze why NKT cells are selectively reduced in autoimmune diseases, and to examine whether nonresponse to α-galactosylceramide (α-GalCer) is due to an abnormality in the antigen-presenting cells (APCs) or NKT cells. 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 α-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 α-GalCer, indicating that patients could be divided into two groups: α-GalCer responders and nonresponders. In contrast, NKT cells from all healthy subjects proliferated against α-GalCer. APCS from all nonresponder patients were found to function as α-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 (α-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 α-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).

Original languageEnglish
Pages (from-to)1127-1138
Number of pages12
JournalArthritis and rheumatism
Volume44
Issue number5
DOIs
Publication statusPublished - May 2001
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

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