Background/Purpose: Myeloid-derived suppressor cells (MDSCs), firstly reported in patients with cancer, have a myeloid origin and an ability to suppress T cell responses. MDSCs are characterized by the co-expression of the myeloid-cell lineage differentiation antigens Gr1 and CD11b. Many investigators have demonstrated that MDSCs promote tumor progression via T cell tolerance in patients with cancers and tumor-bearing mice. However, as for autoimmune diseases, the roles of MDSCs in autoimmune disease remain controversial. Here we investigate the roles of MDSCs in autoimmune arthritis using collagen-induced arthritis (CIA) models.

Methods: CIA was induced in 7-8week-old DBA/1 mice by intradermal injection of 200 μg of bovine type II collagen (CII) in Freund’s complete adjuvant on day 0, followed by a booster injection of 200 μg of CII in Freund’s incomplete adjuvant on day 21. The severity of arthritis in each paw was evaluated 3 times weekly. We first analyzed the number of Gr1⁺ /CD11b⁺ MDSCs in the spleens of mice with CIA by flow cytometry at the onset, the peak, and the convalescence of CIA. Next, MDSCs were isolated from spleens of mice with CIA by magnetic cell separation. Carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeled CD4⁺ T cells were stimulated with anti-CD3/CD28 antibodies (Abs) and cultured in the presence of 30 U/ml interleukin (IL)-2 with or without MDSCs for 5 days. We investigated CD4⁺ T cell proliferation using flow cytometric measurement of CFSE dye dilution. Next, MDSCs were co-cultured with CD4⁺ T cells stimulated with anti-CD3/CD28 Abs for 3 days. We measured cytokines released into supernatant using specific enzyme-linked immunosorbent assay (ELISA).

Results: In a murine arthritis model, MDSCs significantly accumulated in the spleens of mice with CIA at the peak of its severity. MDSCs inhibited the proliferation of CD4⁺ T cells in response to anti-CD3/CD28 Abs in vitro. When we co-cultured CD4⁺ T cells and MDSCs interferon (IFN)-γ and IL-6 released into supernatant were significantly decreased, 97.6 ± 16.1 pg/ml to 79.8 ± 10.1 pg/ml (p < 0.05), 10.4 ± 2.1 pg/ml to 2.9 ± 1.0 pg/ml (p < 0.01), respectively.

Conclusion: MDSCs accumulated in the spleens of mice with CIA. These MDSCs inhibited CD4⁺ T cell proliferation and pro-inflammatory cytokine production in vitro. These findings may indicate the protective roles of MDSCs against autoimmune arthritis�, which could be exploited for new cell-based therapies. We are now investigating the function of MDSCs in vivo.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/myeloid-derived-suppressor-cells-accumulated-in-spleens-of-mice-with-collagen-induced-arthritis-and-inhibited-immune-response-of-cd4-t-cells/