Regulatory T cells in acute dengue viral infection.
Jayaratne E., Wijeratne D., Fernando S., Kamaladasa A., Gomes L., Wijewickrama A., Ogg GS., Malavige GN.
Although regulatory T cells (Tregs) have been shown to be expanded in acute dengue, their role in pathogenesis and their relationship to clinical disease severity, and extent of viraemia have not been fully evaluated. The frequency of Tregs was assessed in 56 adult patients with acute dengue, by determining the proportion of FOXP3 expressing CD4+ CD25+ T cells (FOXP3+ cells). DENV viral loads were measured by quantitative real time PCR and DENV specific T cell responses were measured by ex vivo IFNγ ELISpot assays to overlapping peptide pools of DENV-NS3, NS1 and NS5. CD45RA and CCR4 were used to phenotype different subset of T cells and their suppressive potential was assessed by their expression of CTLA-4 and Fas. While the frequency of FOXP3+ cells, in patients was significantly higher (p<0.0001) when compared to healthy individuals, they did not show any relationship with clinical disease severity or the degree of viraemia. The frequency of FOXP3+ cells did not correlate with either ex vivo IFNγ DENV-NS3, NS5 or NS1 specific T cell responses. The FOXP3+ cells of patients with acute dengue were predominantly CD45RA+ FOXP3low , followed by CD45RA-FOXP3low , with only a small proportion of FOXP3+ cells being of the highly suppressive effector Treg subtype. Expression of CCR4 was also low in the majority of T cells, with only CCR4 only being expressed at high levels in the effector Treg population. Therefore, although FOXP3+ cells are expanded in acute dengue, they predominantly consist of naive Tregs, with poor suppressive capacity. This article is protected by copyright. All rights reserved.