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Open Access Highly Accessed Research article

Identification of myeloid-derived suppressor cells in the synovial fluid of patients with rheumatoid arthritis: a pilot study

Júlia Kurkó15, András Vida1, Tibor T Glant1, Carla R Scanzello23, Robert S Katz4, Anjali Nair2, Zoltán Szekanecz5* and Katalin Mikecz1*

Author Affiliations

1 Section of Molecular Medicine, Department of Orthopedic Surgery, Rush University Medical Center, 1735 W Harrison St, Cohn 712, Chicago, IL 60612, USA

2 Section of Rheumatology, Department of Internal Medicine, Rush University Medical Center, Chicago, IL 60612, USA

3 Division of Rheumatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA

4 Rheumatology Associates, Rush University Medical Center, Chicago, IL 60612, USA

5 Department of Rheumatology, Faculty of Medicine, University of Debrecen, 98 Nagyerdei St, H-4032 Debrecen, Hungary

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BMC Musculoskeletal Disorders 2014, 15:281  doi:10.1186/1471-2474-15-281

Published: 19 August 2014

Abstract

Background

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of innate immune cells with a granulocyte-like or monocyte-like phenotype and a unique ability to suppress T-cell responses. MDSCs have been shown to accumulate in cancer patients, but recent studies suggest that these cells are also present in humans and animals suffering from autoimmune diseases. We previously identified MDSCs in the synovial fluid (SF) of mice with experimental autoimmune arthritis. The goal of the present study was to identify MDSCs in the SF of patients with rheumatoid arthritis (RA).

Methods

RA SF cells were studied by flow cytometry using antibodies to MDSC cell surface markers as well as by analysis of cell morphology. The suppressor activity of RA SF cells toward autologous peripheral blood T cells was determined ex vivo. We employed both antigen-nonspecific (anti-CD3/CD28 antibodies) and antigen-specific (allogeneic cells) induction systems to test the effects of RA SF cells on the proliferation of autologous T cells.

Results

SF from RA patients contained MDSC-like cells, the majority of which showed granulocyte (neutrophil)-like phenotype and morphology. RA SF cells significantly suppressed the proliferation of anti-CD3/CD28-stimulated autologous T cells upon co-culture. When compared side by side, RA SF cells had a more profound inhibitory effect on the alloantigen-induced than the anti-CD3/CD28-induced proliferation of autologous T cells.

Conclusion

MDSCs are present among RA SF cells that are commonly regarded as inflammatory neutrophils. Our results suggest that the presence of neutrophil-like MDSCs in the SF is likely beneficial, as these cells have the ability to limit the expansion of joint-infiltrating T cells in RA.

Keywords:
Rheumatoid arthritis; Myeloid-derived suppressor cells; T cells; Synovial fluid