Peripheral blood but not synovial fluid natural killer T cells are biased towards a Th1-like phenotype in rheumatoid arthritisReportar como inadecuado




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Arthritis Research and Therapy

, 7:R493

First Online: 18 February 2005Received: 13 October 2004Revised: 14 January 2005Accepted: 19 January 2005

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 α-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 α-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 Vα24Vβ11CD3 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.

Abbreviationsα-GalCerα-galactosylceramide

FITCfluorescein isothiocyanate

IFNinterferon

ILinterleukin

NKTnatural killer T cell

PBMCperipheral blood mononuclear cell

PEphycoerythrin

PCRpolymerase chain reaction

RArheumatoid arthritis

SFMCsynovial fluid mononuclear cell

TCRT-cell receptor

ThT-helper cell.

Electronic supplementary materialThe online version of this article doi:10.1186-ar1695 contains supplementary material, which is available to authorized users.

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Autor: Loes Linsen - Marielle Thewissen - Kurt Baeten - Veerle Somers - Piet Geusens - Jef Raus - Piet Stinissen

Fuente: https://link.springer.com/







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