Date: Sunday, November 8, 2015
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose: Inducible costimulator (ICOS) is an immunostimulatory receptor that belongs to the CD28/CTLA4 family. ICOSL (ICOS ligand), which belongs to the B7 family, is the ligand for ICOS and is crucial for T helper cell and B cell differentiation. The costimulatory signal of ICOS/ICOSL in T cell/antigen presenting cell interactions might be involved the pathogenesis of systemic lupus erythematosus (SLE). Clinical trial of monoclonal antibody targeting ICOSL in SLE is underway. However, the expression of ICOSL and the role of ICOS/ICOSL signaling in the interactions between T cells in the pathogenesis of SLE are not well characterized. We investigate the expression and function of the ICOSL on T cells in patients with SLE
Methods: To investigate the expression of the ICOSL on CD 4+ T cells, we evaluated surface ICOSL expression on CD4+ T cells in peripheral blood (PB) from 24 patients with SLE, PB from 15 healthy controls using flow cytometry. We also evaluated soluble ICOSL expression in the plasma of 24 patients with SLE and 14 healthy controls. To explore the role of ICOS/ICOSL signaling in CD4+ T cells in SLE, we examined CD4+ T cell proliferation from seven patients with SLE. After blockade of the ICOS/ICOSL signal using anti-ICOSL antibody or ICOS immunoglobulin, CD4+ T cell proliferation in response to treatment with anti-CD3 antibody was evaluated. During the proliferation assay, cytokine levels (ILF-gamma, TNF-alpha and IL-17) in the CD4+ T cell culture supernatants were assessed.
Results: The proportion of ICOSL+ CD 4+ T cells was significantly increased in the PB of patients with SLE (13.6 ± 7.6%, range 3~29%) as compared with the level observed in the PB of healthy controls (1.3 ± 1.2 %, range 0~4%, P < 0.01). The soluble ICOSL protein level in patients with SLE was significantly higher than that of healthy controls (43.0 ± 39.2 pg/mL vs 2.0± 2.9 pg/mL,P < 0.01). The level of soluble ICOSL protein correlated with surface ICOSL expression on the CD4+ T cells (γ =0.69, P<0.01). After blocking of the ICOS/ICOSL pathway, the suppression of CD4+ T cell proliferation was not significantly different between the two treatment groups (ICOS immunoglobulin and anti-ICOSL antibody) and the control groups. The expression level of TNF-alpha and IL-17 were also significantly depressed in the treatment groups (ICOS immunoglobulin) compared to the control groups.
Conclusion: In this study, we found that ICOSL, a ligand of ICOS, was significantly up-regulated on CD4+ T cells in the PB in patients with SLE. In addition, blockade of ICOS/ICOSL signaling suppressed the expression of TNF–alpha and IL-17 but it did not affect CD4+ T cell proliferation. Our results support a contribution of the ICOS/ ICOSL pathway to the pathogenesis of SLE.
To cite this abstract in AMA style:Her M, Kim D, Park J, Han D. Expression of Inducible Costimulator Ligand (ICOSL) on CD4+ T Cells in Patients with Systemic Lupus Erythematosus [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/expression-of-inducible-costimulator-ligand-icosl-on-cd4-t-cells-in-patients-with-systemic-lupus-erythematosus/. Accessed January 17, 2021.
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