Peripheral blood but not synovial fluid natural killer T cells are biased towards a Th1-like phenotype in rheumatoid arthritis |
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Authors: | Loes?Linsen Marielle?Thewissen Kurt?Baeten Veerle?Somers Piet?Geusens Jef?Raus Email author" target="_blank">Piet?StinissenEmail author |
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Institution: | (1) Biomedisch Onderzoeksinstituut, Limburgs Universitair Centrum and School of Life Sciences, Universitaire Campus, Transnationale Universiteit Limburg, Diepenbeek, Belgium |
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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 Vα24+Vβ11+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. |
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