Expression of TIM‐3 on CD4+ and CD8+ T cells in the peripheral blood and synovial fluid of rheumatoid arthritis

Abstract

Rheumatoid arthritis (RA) is characterized by a chronic inflammatory process that targets the synovial lining of diarthrodial joints. TIM-3 plays a key role in the negative regulation of the immune response. In this study, we investigated the expression of TIM-3 on CD4+ and CD8+ T cells from systemic (peripheral blood) and local (synovial fluid) perspectives of RA. Level of TIM-3+ cells from peripheral blood and synovial fluid of patients as well as peripheral blood of healthy controls was measured by flow cytometry. Results showed that TIM-3 expression was significantly increased in both CD4+ and CD8+ T cells in the peripheral blood of RA (p < 0.001 and p < 0.001, respectively). Furthermore, patients revealed even higher expression of TIM-3 in CD4+ and CD8+ T cells in synovial fluid than in peripheral blood. When comparing TIM-3 level with the severity of RA, we identified that the percentage of TIM-3 on both peripheral CD4+ and peripheral CD8+ T cells was negatively correlated with disease activity score 28 (DAS28) of the patients. Similarly, TIM-3 on synovial fluid CD4+ and CD8+ T cells also revealed inverse correlation with DAS28 of the cases. Our data demonstrate a negative correlation between TIM-3 and the disease progression of RA.

Increased Expression and Modulated Regulatory Activity of Coinhibitory Receptors PD‐1, TIGIT, and TIM‐3 in Lymphocytes From Patients With Systemic Sclerosis

“…Li et al observed increased levels of TIM-3 on CD4+ and CD8+ T cells in the peripheral blood of patients with rheumatoid arthritis (39), whereas our study showed no changes in TIM-3 in SSc T cell subsets, but did show an increase in NK cells ( Figure 1E). In lupus patients, the levels of TIGIT were found to be up-regulated on CD4+ T cells but reduced in CD8+ T cells, NK cells, and Treg cells (40), an expression pattern that does not match with our observations in patients with SSc ( Figure 1D).…”

“…In addition, serum levels of soluble forms of PD-1 and its ligand PD-L2 were recently shown to be elevated in SSc (14). Li et al describe increased TIM-3 on CD4 + and CD8 + T cells in peripheral blood from rheumatoid arthritis patients (39), while our data show no changes in TIM-3 in SSc T cell subsets, but an increase in NK cells (Fig. 1E).…”

Elevated Expression of Immunoreceptor Tyrosine-Based Inhibitory Motif (TIGIT) on T Lymphocytes is Correlated with Disease Activity in Rheumatoid Arthritis

“…Programmed cell death-1 (PD1), an immunosuppressive co-stimulatory molecule proven to play a major role in suppressing immune responses, and its ligand, programmed cell death-ligand 1, were found to be elevated in the T cells of patients with RA [12,13]. T cell immunoglobulin domain- and mucin-domain-containing molecule-3 (Tim-3), which are inhibitory receptors, have been showed to be expressed on T cells with high levels and to be correlated with disease activity in patients with RA [14]. Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), a member of the immunoglobulin superfamily that can down-regulate T-cell function, was also reported to be decreased on T cells, and its dysfunction was identified as a potential cause for abnormal T cell activation in RA [16].…”

Tim‐3 and its role in regulating anti‐tumor immunity

“…In patients with rheumatoid arthritis (RA), Tim‐3 expression on CD4 + and CD8 + T cells in peripheral blood mononuclear cells (PBMCs) and synovial fluid was increased. But the percentage of Tim‐3 expression on peripheral CD4 + and CD8 + T cells was negatively correlated with disease severity, as measured by the disease activity score 28 (DAS28) of the patients . In addition, the level of Tim‐3 expression on T cells was also inversely correlated with plasma TNF levels.…”