Altered profile of regulatory T cells and associated cytokines in mild and moderate dengue.

Abstract

The pathogenesis of dengue is immune-mediated. Regulatory T cells suppress immune response and may contribute to better prognosis. The present study evaluates Tregs and cytokines in dengue patients in the context of disease severity, time of sampling and immune status. The cohort included 90 patients (51 mild, 39 moderate) and 27 healthy controls. Frequencies of Tregs, CD4(+)CD25(-)Foxp3(+) T cells and CD3(+), CD3(+)CD4(+) and CD3(+)CD8(+) T cells were enumerated by flow cytometry. Circulating levels of 15 cytokines/chemokines were measured using Luminex technology and mRNA levels of Foxp3, IL-10 and TGF-β were assessed by real-time polymerase chain reaction (PCR). Significantly higher frequencies of Tregs were observed in mild cases, especially during post-defervescence. The difference between mild and moderate cases was more evident in secondary infections. Frequencies of T cells were higher in mild cases but during pre-defervescence. On the other hand, the levels of IL-6, IL-7, IL-8, TNF-α and IL-10 were significantly higher in moderate cases. IL-6 and IL-8 levels correlated negatively with Treg frequencies during post-defervescence and in secondary infections. Higher levels of IL-10 and TGF-β in moderate cases were not reflected by their corresponding mRNA levels. Platelet counts correlated positively with Treg frequencies and TGF-β levels, and negatively with IL-10 levels. Higher Treg frequencies may favour a beneficial outcome in dengue. Higher cytokine levels may indirectly contribute to disease severity by exerting an inhibitory influence on Tregs. The dichotomy between mRNA and proteins levels for IL-10 and TGF-β is suggestive of increased translational efficiency.