CD39⁺ EXPRESSION BY REGULATORY T CELLS IN PULMONARY SARCOIDOSIS AND LOFGREN’S SYNDROME

Abstract

Sarcoidosis is a disorder of unknown etiology characterized by development of necrosis-free epithelioid cell granulomas in various tissues. There are two main phenotypes of pulmonary sarcoidosis (PS): Lofgren’s syndrome (LS) is an acute form with favorable outcome, while non-Lofgren’s syndrome (nLS) is a chronic type of disease that can lead to pulmonary fibrosis in 20% of cases.Our study was aimed at investigating changes in the main cell-surface differentiation antigens on peripheral blood regulatory T cells (Tregs) from the patients with first diagnosed PS without treatment (LS, n = 11) and nLS (n = 46) compared to healthy volunteers (HC, n = 26).These indexes might be used as immunological markers for predicting severity of this disorder. Flow cytometry analysis of peripheral blood cell samples demonstrated that the nLS patients had decreased relative numbers of CD3+ cells vs healthy controls, as well as diminished CD3+CD4+ cells vs HC and LS patients. Furthermore, the relative and absolute Treg numbers were also decreased in nLS group vs HC (2.83% (2.47; 3.36) vs 3.33% (2.79; 3.84), p = 0.021), and 37 (29; 52) cells vs 50 (42; 65), p = 0.004, respectively) per one microliter of peripheral blood. Relative number of CD39-positive Тregs in chronic vs acute sarcoidosis patients was associated with 51.02% (38.20; 61.62) vs 48.64% (41.46; 63.72) that was significantly (p < 0.001 and p = 0.007, respectively) higher than in HC (39.52% (11.55; 46.34). We have found that “naïve” (CD45R0-CD62L+) Тregs did not significantly differ in percentage of CD39- and CD73-positive cells in all the groups tested. Moreover, CD45R0+CD62L+ Тregs in LS and nLS patients contained significantly more CD39-positive cells (69.66% (61.92; 79.34) and 67.62% (61.92; 79.34), respectively, compared to 47.55% (15.74; 65.32) in HC (p < 0.001 and p = 0.004, respectively). In case of CD45R0 + CD62LTregs able to exit from the circulation and migrate to the site of inflammation, an increased percentage of CD39-positive subset was noted only in patients with chronic sarcoidosis and HC (61.79% (55.12; 73.09) and 57.27% (16.03; 66.98), p = 0.006). Enhanced CD39 expression on Tregs seems to be related to chronic immune response, so that antigen elimination becomes impossible due to Treg overactivation, as shown in patients with sarcoidosis and some other chronic autoimmune and infectious disorders.

FOXP3+ regulatory T cells are associated with the severity and prognosis of sarcoidosis

“…Ki-67, a marker of recent cell division, was upregulated in sarcoidosis PBMCs, in CD4 + and CD8 + T cells, and most substantially in Tregs ( Figure 1C ), suggesting ongoing clonal activation of T cells with compensatory division of Tregs. In contrast to previously reported data ( 4 , 14 , 15 ), we found that the CD45RO effector/memory subset in sarcoidosis Tregs was decreased, with no differences in expression of CTLA-4 and CD39 ( Supplementary Figures S2B–D ). CXCR5 was upregulated in sarcoidosis Tregs and CD8 + cells, but CD4 + CXCR5 + T follicular helper cell numbers were not affected ( Supplementary Figure S2E ).…”

Features of cytokine profile in patients with sarcoidosis

“…Ранее нами был проведен анализ содержания некоторых популяций и субпопуляций Т-и В-лимфоцитов при саркоидозе. Описано содержание на разных стадиях дифференцировки цитотоксических Т-лимфоцитов, особенностей состава регуляторных Т-лимфоцитов, а также изменение субпопуляционного состава В-лимфоцитов в периферической крови больных саркоидозом при разной степени активности заболевания [1,4,5,6,7]. Известно, что направленную миграцию клеток в ткани обеспечивают лиганды для определенных рецепторов, экспрессирующихся на клеточной мембране.…”

Sarcoidosis and Autoimmune Inflammatory Syndrome Induced by Adjuvants

“…[84]. When comparing the level of expression of CD39 on regulatory T-cells of peripheral blood, it turned out that the relative content of CD39 + cells is increased both in patients with acute onset and in primary chronic sarcoidosis [85]. It is likely that the formation of anti-inflammatory adenosine, which is involved in the suppression of hypersensitive immune responses, is one of the key and most common mechanisms of immunosuppression in both acute and chronic sarcoidosis.…”