The number and activity of CD3⁺TCR Vα7.2⁺CD161⁺ cells are increased in children with acute rheumatic fever

Background: Acute rheumatic fever (ARF) is an autoimmune disease caused by group A β-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 (MAIT) 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⁺TCRVα7.2⁺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⁺CD161⁺TCRVα7.2⁺ cells and IFN-γ and TNF-α production were quantified by Flow cytometry.

Results: Acute and recovered ARF patients had significantly elevated the number of CD3⁺TCRVα7.2⁺CD161⁺ cells in their PB. Both CD4⁺ and CD4^- subsets were increased. Moreover, total CD3⁺TCRVα7.2⁺CD161⁺ cell numbers were significantly higher in the recovered patients' PB compared with active ARF patients. In addition, CD3⁺TCRVα7.2⁺CD161⁺ cells in both acute and recovered patients produced significantly more IFN-γ and TNF-α. Non-MAIT 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-γ and TNF-α.

Conclusion: Our data reveal that CD3⁺TCRVα7.2⁺CD161⁺ cells are elevated and actively producing IFN-γ and TNF-α in acute and recovered ARF patients and may contribute to ARF pathology.