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.
