The Number and Activity of Cd3+tcr Vα7.2+cd161+< Cells Are Increased in Children With Acute Rheumatic Fever

Abstract

Background: Acute rheumatic fever (ARF) is an autoimmune disease caused by group A beta-hemolytic streptococci (GAS) and may develop into rheumatic heart disease (RHD). The pathogenesis of ARF and RHD involves molecular mimicry and antibody-mediated mechanisms. T cell involvement is described in various stages of the disease. Mucosal associated invariant T (MATT) cells are enriched at the mucosa and are present in the blood and may be activated by GAS. Methods: In this study, we investigated the quantity and activity of CD3(+) TCRV alpha 7.2(+) CD161(+) cells in the active and recovered ARF patients and healthy controls. Twenty newly diagnosed, 20 recovered-ARF children, and 20 healthy controls were enrolled in the study. Peripheral blood (PB) mononuclear cells were isolated by Ficoll-Paque density gradient. CD4(+) CD4(-) subsets of CD3(+) TCRV alpha 7.2(+) CD161(+) cells and IFN-gamma and TNF-alpha production were quantified by Flow cytometry. Results: Acute and recovered ARF patients had significantly elevated the number of CD3(+) TCRV alpha 7.2(+) CD161(+) cells in their PB. Both CD4(+) and CD4(-) subsets were increased. Moreover, total cell numbers were significantly higher in the recovered patients PB compared with active ARE patients. In addition, CD3(+) TCRV alpha 7.2(+) CD161(+) cells in both acute and recovered patients produced significantly more IFN-gamma and TNF-alpha. Non-MALT total CD3(+) T cell, CD4(+) and CD4(-) T cell subsets were also increased in active and recovered ARF patients and they also produced more IFN-gamma and TNF-alpha. Conclusion: Our data reveal that CD3(+) TCRV alpha 7.2(+) CD161(+) cells are elevated and actively producing IFN-gamma and TNF-alpha in acute and recovered ARF patients and may contribute to ARF pathology. (C) 2021 Elsevier B.V. All rights reserved.