No abstract

SUMMARY Dengue virus (DENV) can cause diseases ranging from dengue fever (DF) to more severe dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). Whether antiviral T cells contribute to the protection against or pathogenesis of severe disease is not well defined. Here, we identified antigen-specific IL-10+IFN-γ+ double-positive (DP) CD4 T cells during acute DENV infection. While the transcriptomic signatures of DP cells partially overlapped with those of cytotoxic and type 1 regulatory CD4 T cells, the majority of them were non-cytotoxic/Tr1 and included IL21, IL22, CD109, and CCR1. Although we observed a higher frequency of DP cells in DHF, the transcriptomic profile of DP cells was similar in DF and DHF, suggesting that DHF is not associated with the altered phenotypic or functional attributes of DP cells. Overall, this study revealed a DENV-specific DP cell subset in patients with acute dengue disease and argues against altered DP cells as a determinant of DHF.

Upon Ag encounter, T cells can rapidly divide and form an effector population, which plays an important role in fighting acute infections. In humans, little is known about the molecular markers that distinguish such effector cells from other T cell populations. To address this, we investigated the molecular profile of T cells present in individuals with active tuberculosis (ATB), where we expect Ag encounter and expansion of effector cells to occur at higher frequency in contrast to Mycobacterium tuberculosis–sensitized healthy IGRA+ individuals. We found that the frequency of HLA-DR+ cells was increased in circulating CD4 T cells of ATB patients, and was dominantly expressed in M. tuberculosis Ag–specific CD4 T cells. We tested and confirmed that HLA-DR is a marker of recently divided CD4 T cells upon M. tuberculosis Ag exposure using an in vitro model examining the response of resting memory T cells from healthy IGRA+ to Ags. Thus, HLA-DR marks a CD4 T cell population that can be directly detected ex vivo in human peripheral blood, whose frequency is increased during ATB disease and contains recently divided Ag-specific effector T cells. These findings will facilitate the monitoring and study of disease-specific effector T cell responses in the context of ATB and other infections.

Allele frequencies and forensically important parameters of ten autosomal miniSTR loci, D1S1677, D2S1776, D10S1248, D11S4463, D12SATA, D14S1434, D17S974, D18S853, D20S482, and D22S1045, were obtained for 278 unrelated adults from the Sri Lankan population. The combined power of discrimination and probability of exclusion was found to be 0.999999999621539 and 0.9979620, respectively. No significant deviations from Hardy-Weinberg equilibrium were observed except for D20S482 which conformed to HW expectations only after the application of a Bonferroni correction. The study suggests the potential use of these miniSTRs as a supplement or as a stand-alone STR marker system for the analysis of highly degraded evidence in Sri Lanka.