Proliferatory defect of invariant population and accumulation of non-invariant CD1d-restricted natural killer T cells in the joints of RA patients

Abstract

Objectives. While numerical and functional defects of invariant NKT cells have been demonstrated in rheumatoid arthritis (RA), the detailed characterization of proliferative and secretory responses following CD1d-mediated presentation is lacking; the presence of non-invariant populations has never been assessed in human autoimmunity. We have evaluated both invariant and non-invariant populations in the blood and synovial fluid from patients to assess feasibility of NKT cell-directed manipulations in RA.

Methods. NKT cell populations were quantified by anti-CD4/anti-Vα24 staining and/or CD1d tetramers. Proliferation was measured in cultures of mononuclear cells following stimulations with αGalCer and cytokine secretion determined by multi-bead assay.

Results. We have confirmed a proliferative defect of iNKT cells in both peripheral blood and synovial fluid from RA patients, but no changes in baseline frequencies. Moreover, we have detected an enlargement of non-invariant cell pool in synovial fluid samples. In addition, we noted an evident Th2 shift following exposure to αGalCer and pronounced IL-6 secretion.

Conclusions. While RA patients suffer from defective proliferative responses of invariant NKT cells, non-invariant cells accumulate at the site of inflammation. While stimulation with αGalCer results in reduced TNF-α and increased suppressive IL-10, abundantly produced IL-6 could potentially contribute to the induction of Th17 cells in the joints.

Keywords:

• Autoimmunity
• CD1d
• Rheumatoid arthritis
• αGalCer
• NKT cells
• Vα24⁺ cells

Acknowledgements

We are grateful to the patients and healthy controls for participating in this study, Dr. RN. Thompson, Dr. C. Estrach and the research nurses for collecting patients’ samples and Dr E. Naylor for technical help with the multi-bead assay.

Funding

This work was supported in part by an Arthritis Research UK Project Grant [P0571], a Wellcome Leave Clinical Fellowship [GR061125] and Internal Rheumatology Studentship from the University of Liverpool.

Conflicts of interest

Authors declare no conflicts of interests.