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Activation of Peripheral T Follicular Helper Cells During Acute Dengue Virus Infection.

ABSTRACT: Background:Follicular helper T cells (TFH) are specialized CD4 T cells required for B-cell help and antibody production. Methods:Given the postulated role of immune activation in dengue disease, we measured the expansion and activation of TFH in the circulation (peripheral TFH [pTFH]) collected from Thai children with laboratory-confirmed acute dengue virus (DENV) infection. Results:We found significant expansion and activation of pTFH subsets during acute infection with the highest frequencies of activated pTFH (PD1hi pTFH and PD1+CD38+ pTFH) detected during the critical phase of illness. Numbers of activated pTFH were higher in patients with secondary compared with primary infections and in patients with more severe disease. We also found a positive correlation between the frequencies of activated pTFH and the frequencies of plasmablasts. Conclusions:To our knowledge, this is the first ex vivo analysis of pTFH activation during acute DENV infection. Overall, our study supports the model that pTFH contribute to disease evolution during the critical stage of illness.

SUBMITTER: Haltaufderhyde K

PROVIDER: S-EPMC6927865 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Activation of Peripheral T Follicular Helper Cells During Acute Dengue Virus Infection.

Haltaufderhyde Kirk K Srikiatkhachorn Anon A Green Sharone S Macareo Louis L Park Sangshin S Kalayanarooj Siripen S Rothman Alan L AL Mathew Anuja A

The Journal of infectious diseases 20181001 10

<h4>Background</h4>Follicular helper T cells (TFH) are specialized CD4 T cells required for B-cell help and antibody production.<h4>Methods</h4>Given the postulated role of immune activation in dengue disease, we measured the expansion and activation of TFH in the circulation (peripheral TFH [pTFH]) collected from Thai children with laboratory-confirmed acute dengue virus (DENV) infection.<h4>Results</h4>We found significant expansion and activation of pTFH subsets during acute infection with th ...[more]

PMID: 29917084

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Project description:BackgroundThe association of functionality and phenotype of follicular helper T cells (Tfh) with dengue virus (DENV) specific antibody responses and clinical disease severity has not been well studied.MethodsWe investigated the phenotype and functionality of Tfh cells and plasmablasts in adult patients (DF = 18, DHF = 22) with acute dengue (day 4 to 8 since onset of fever) of varying severity using multiparametric flowcytometry. The properties of Tfh cells were correlated with viraemia, disease severity, plasmablast responses and DENV-specific serum antibody responses. We further evaluated the kinetics of neutralizing antibodies (Neut50) throughout the course of illness in order to evaluate their association with clinical disease severity and viraemia.ResultsTfh cells (especially those producing IL-21 and co-expressing PD-1 and ICOS) were found to be significantly expanded (p < 0.0001) and highly activated in patients with DHF compared to those with DF. The frequency of Tfh cells significantly correlated with DENV-specific IgG, NS1-specific antibodies and Neut50 antibody titres in patients with DHF but not in those with DF. Although the Neut50 titres increased during the course of acute secondary DENV infection, they showed differences based on serotype. For instance, the Neut50 titres were significantly higher during the latter part of illness in patients with DF compared to DHF in DENV1 infection, while in DENV2, patients with DHF had significantly higher titres. The viral loads during early illness did not correlate with the subsequent rise in the Neut50 antibody titres during any time point of illness.ConclusionsThe expansion of Tfh cells is associated with DHF and DENV-specific IgG, NS1-specific and neutralizing antibodies. Neut50 titres did not associate with disease severity or viraemia at the point of first presentation during the febrile phase, but later titres do show differential association with severity in patients with DENV1 compared to DENV2.

Dataset Information

Activation of Peripheral T Follicular Helper Cells During Acute Dengue Virus Infection.

Publications

Activation of Peripheral T Follicular Helper Cells During Acute Dengue Virus Infection.

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