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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/2132

Title: Peripheral blood but not synovial fluid natural killer T cells are biased towards a Th1-like phenotype in rheumatoid arthritis
Authors: LINSEN, Loes
SOMERS, Veerle
Issue Date: 2005
Citation: ARTHRITIS RESEARCH & THERAPY, 7(3). p. R493-R502
Abstract: Natural killer T (NKT) cells have been implicated in the regulatory immune mechanisms that control autoimmunity. However, their precise role in the pathogenesis of rheumatoid arthritis (RA) remains unclear. The frequency, cytokine profile and heterogeneity of NKT cells were studied in peripheral blood mononuclear cells (PBMCs) from 23 RA patients and 22 healthy control individuals, including paired PBMC-synovial fluid samples from seven and paired PBMC-synovial tissue samples from four RA patients. Flow cytometry revealed a decreased frequency of NKT cells in PBMCs from RA patients. NKT cells were present in paired synovial fluid and synovial tissue samples. Based on the reactivity of PBMC-derived NKT cells toward alpha-galactosylceramide, RA patients could be divided into responders (53.8%) and nonresponders (46.2%). However, NKT cells isolated from synovial fluid from both responders and nonresponders expanded upon stimulation with alpha-galactosylceramide. Analysis of the cytokine profile of CD4(+) and CD4(-) PBMC derived NKT cell lines from RA patients revealed a significantly reduced number of IL-4 producing cells. In contrast, synovial fluid derived NKT cell lines exhibited a Th0-like phenotype, which was comparable to that in healthy control individuals. This suggests that synovial fluid NKT cells are functional, even in patients with nonresponding NKT cells in their blood. We conclude that, because the number of V alpha 24(+)V beta 11(+)CD3(+) NKT cells is decreased and the cytokine profile of blood-derived NKT cells is biased toward a Th1-like phenotype in RA patients, NKT cells might be functionally related to resistance or progression of RA. Providing a local boost to the regulatory potential of NKT cells might represent a useful candidate therapy for RA.
Notes: Limburgs Univ Ctr, Biomed Onderzoeksinst, Diepenbeek, Belgium. Transnat Univ Limburg, Sch Life Sci, Diepenbeek, Belgium.Stinissen, P, Limburgs Univ Ctr, Biomed Onderzoeksinst, Univ Campus, Diepenbeek, Belgium.piet.stinissen@luc.ac.be
URI: http://hdl.handle.net/1942/2132
DOI: 10.1186/ar1695
ISI #: 000230336300018
ISSN: 1478-6362
Category: A1
Type: Journal Contribution
Validation: ecoom, 2006
Appears in Collections: Research publications

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