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Functionality of dengue virus specific memory T cell responses in individuals who were hospitalized or who had mild or subclinical dengue infection.

Abstract：

BACKGROUND:Although antibody responses to dengue virus (DENV) in naturally infected individuals have been extensively studied, the functionality of DENV specific memory T cell responses in relation to clinical disease severity is incompletely understood. METHODOLOGY/PRINCIPAL FINDINGS:Using ex vivo IFNγ ELISpot assays, and by determining cytokines produced in ELISpot supernatants, we investigated the functionality of DENV-specific memory T cell responses in a large cohort of individuals from Sri Lanka (n=338), who were naturally infected and were either hospitalized due to dengue or had mild or sub clinical dengue infection. We found that T cells of individuals with both past mild or sub clinical dengue infection and who were hospitalized produced multiple cytokines when stimulated with DENV-NS3 peptides. However, while DENV-NS3 specific T cells of those with mild/sub clinical dengue infection were more likely to produce only granzyme B (p=0.02), those who were hospitalized were more likely to produce both TNFα and IFNγ (p=0.03) or TNFα alone. We have also investigated the usefulness of a novel T cell based assay, which can be used to determine the past infecting DENV serotype. 92.4% of DENV seropositive individuals responded to at least one DENV serotype of this assay and none of the seronegatives responded. Individuals who were seronegative, but had received the Japanese encephalitis vaccine too made no responses, suggesting that the peptides used in this assay did not cross react with the Japanese encephalitis virus. CONCLUSIONS/SIGNIFICANCE:The types of cytokines produced by DENV-specific memory T cells appear to influence the outcome of clinical disease severity. The novel T cell based assay, is likely to be useful in determining the past infecting DENV serotype in immune-epidemiological studies and also in dengue vaccine trials.

journal_name

PLoS Negl Trop Dis

journal_title

PLoS neglected tropical diseases

authors

Jeewandara C,Adikari TN,Gomes L,Fernando S,Fernando RH,Perera MK,Ariyaratne D,Kamaladasa A,Salimi M,Prathapan S,Ogg GS,Malavige GN

doi

10.1371/journal.pntd.0003673

subject

Has Abstract

pub_date

2015-04-13 00:00:00

pages

e0003673

issue

eissn

1935-2727

issn

1935-2735

pii

PNTD-D-14-02194

journal_volume

pub_type

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Functionality of dengue virus specific memory T cell responses in individuals who were hospitalized or who had mild or subclinical dengue infection.