Background/Purpose:

Recent studies have showed that quantitative and/or functional abnormalities of the regulatory T cells (Tregs) may play a vital role in the development of rheumatoid arthritis (RA). It is reported that CD25⁺FOXP3⁺T cells include CD4⁺CD25⁺FOXP3⁺T (CD4⁺Tregs) and CD8⁺CD25⁺FOXP3⁺T cells (CD8⁺ Tregs). CD8⁺Tregs also have been showed even stronger immunosuppressive function and more sensitive to IL-2 than CD4⁺Tregs in vivo.

Our study was designed to clarify the level of peripheral CD8⁺T cell subsets in RA patients, especially CD4^–(CD8⁺)CD25⁺FOXP3⁺T cells, and to investigate the role of recombinant human interleukin-2 (IL-2) in the regulation of CD4^–(CD8⁺)CD25⁺FOXP3⁺ T cells in RA patients to provide a basis to IL-2 therapy.

Methods:

Total 231 Patients with RA were enrolled, including 75 new-onset RA and 156 treated with low dose IL-2 (50 WIU/day for 5 days, subcutaneous injection), and 90 healthy adults were included as controls. The clinical data of RA patients were collected, including gender, age, joint swelling, tenderness and so on. And laboratory parameters were erythrocyte sedimentation rate (ESR), C reactive protein (CRP), rheumatoid factor(RF) and anti-cyclic citrullinated peptide antibody (Anti-CCP). At the same time, the DAS28 score of RA group was calculated. The absolute number of CD4^–CD25⁺FOXP3⁺ T cells in peripheral blood were detected by flow cytometry. We assume that CD4^– T cells with CD25⁺ and FOXP3⁺ were mostly CD8⁺CD25⁺FOXP3⁺ T cells, i.e. 8⁺Tregs.

Results:

As compared with the healthy controls, the absolute number of CD8⁺ Treg cells decreased significantly in the new-onset RA patients [0.92(0.42,1.39) vs 1.31(0.72,2.52), P <0.001]. The absolute number of CD8⁺Treg cells was significantly negative correlated with tenderness joints, DAS28 score and RF, (r=-0.249, P=0.032; r=-0.294, P=0.010; r=-0.365, P=0.001); The absolute number of CD8⁺ Treg cells was no significantly correlated the swelling of the joints, ESR, CRP, Anti-CCP antibody (r=-0.199, P=0.087; r=-0.202, P=0.082; r=0.008, P=0.947; r=-0.083, P=0.480). After treatment with IL-2, the absolute number of CD8⁺ Treg cells increased significantly as compared with that before treatment [0.88(0.42,1.51) vs 1.98(0.91,3.37), P<0.001].

Conclusion:

The absolute number of CD8⁺ Treg cells in initial diagnosed patients was lower than that of healthy controls, implying that the immunosuppressive function was attenuated by disease itself, rather than immunosuppression therapy, which may be an important factor in the pathogenesis of RA. Low dose IL-2 can expand CD8⁺Treg cells in peripheral blood, and thereby improve the immune function, so that RA patients were relieved. We are about to detect CD8⁺Treg cells using more accurate technique to verify this theory.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/changes-of-cd4-cd8-regulatory-t-cells-in-rheumatoid-arthritis-patients-and-during-interleukin-2-therapy/