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

Abstract

BackgroundMyeloid-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).MethodsRA 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.ResultsSF 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.ConclusionMDSCs 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.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2474-15-281) contains supplementary material, which is available to authorized users.

Suppression of Proteoglycan-Induced Autoimmune Arthritis by Myeloid-Derived Suppressor Cells Generated In Vitro from Murine Bone Marrow

“…Most recently, we identified granulocytic MDSCs in the SF of RA patients; these RA SF-MDSCs moderately suppressed the anti-CD3/CD28-induced proliferation of autologous T cells, but potently suppressed alloAg-induced T-cell proliferation in vitro [51]. It is likely that SF-MDSCs inhibit the expansion of joint-homing (pathogenic) T cells in both RA and animal models of the disease.…”

Chronic Active Arthritis Driven by Macrophages Without Involvement of T Cells

“…It will also be important to understand the interplay between macrophages and fibroblasts, particularly because fibroblasts are critical in the TNF-transgenic model of RA (47). Another interesting cell type to address would be monocytic myeloid-derived suppressor cells (CD11b+Ly-6C+), which also have been found in RA patients and that possibly could be a source of ROS in this model (48). In fact, we have previously shown an increase in the number of myeloid-derived suppressor cells in a recombinant Ncf1 mouse, which decreased after Ncf1 induction both in the early stages and in the later stages of arthritis (49).…”

Neutrophils Slow Disease Progression in Murine Lupus via Modulation of Autoreactive Germinal Centers

“…Although neutrophils have been shown to act in an immunosuppressive capacity during chronic inflammatory conditions such as malignancy or viral infection, the possibility that a pro-resolving or protective neutrophil is present in lupus has only recently been proposed (15, 16, 36–39). In an amyloid-induced lupus model neutrophil depletion worsened disease similar to our findings.…”