Phenotype and functionality of follicular helper T cells in patients with acute dengue infection

Journal of Biomedical Science - 2020
Ayesha Wijesinghe1, Jayani Gamage1, Hemantha Goonewardena1, Laksiri Gomes1, Deshni Jayathilaka1, Dulharie T. Wijeratne1, Ruklanthi de Alwis2,3, Chandima Jeewandara1, Ananda Wijewickrama4, Graham Ogg5, Gathsaurie Neelika Malavige1,5
1Centre for Dengue Research, University of Sri Jayewardenepura, Nugegoda, Sri Lanka
2Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore
3Viral Research & Experimental Medicine Centre, SingHealth/Duke-NUS, Singapore, Singapore
4National Institute of Infectious Diseases, Angoda, Sri Lanka
5MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford, UK

Tóm tắt

Abstract Background

The 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.

 Methods

We 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.

 Results

Tfh 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.

 Conclusions

The 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.

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