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CD8 T cells protect adult naive mice from JEV-induced morbidity via lytic function.

ABSTRACT: Following Japanese encephalitis virus (JEV) infection neutralizing antibodies are shown to provide protection in a significant proportion of cases, but not all, suggesting additional components of immune system might also contribute to elicit protective immune response. Here we have characterized the role of T cells in offering protection in adult mice infected with JEV. Mice lacking ?/?-T cells (TCR?-null) are highly susceptible and die over 10-18 day period as compared to the wild-type (WT) mice which are resistant. This is associated with high viral load, higher mRNA levels of proinflammatory cytokines and breach in the blood-brain-barrier (BBB). Infected WT mice do not show a breach in BBB; however, in contrast to TCR?-null, they show the presence of T cells in the brain. Using adoptive transfer of cells with specific genetic deficiencies we see that neither the presence of CD4 T cells nor cytokines such as IL-4, IL-10 or interferon-gamma have any significant role in offering protection from primary infection. In contrast, we show that CD8 T cell deficiency is more critical as absence of CD8 T cells alone increases mortality in mice infected with JEV. Further, transfer of T cells from beige mice with defects in granular lytic function into TCR?-null mice shows poor protection implicating granule-mediated target cell lysis as an essential component for survival. In addition, for the first time we report that ?/?-T cells also make significant contribution to confer protection from JEV infection. Our data show that effector CD8 T cells play a protective role during primary infection possibly by preventing the breach in BBB and neuronal damage.

SUBMITTER: Jain N

PROVIDER: S-EPMC5308832 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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CD8 T cells protect adult naive mice from JEV-induced morbidity via lytic function.

Jain Nidhi N Oswal Neelam N Chawla Amanpreet Singh AS Agrawal Tanvi T Biswas Moanaro M Vrati Sudhanshu S Rath Satyajit S George Anna A Bal Vineeta V Medigeshi Guruprasad R GR

PLoS neglected tropical diseases 20170202 2

Following Japanese encephalitis virus (JEV) infection neutralizing antibodies are shown to provide protection in a significant proportion of cases, but not all, suggesting additional components of immune system might also contribute to elicit protective immune response. Here we have characterized the role of T cells in offering protection in adult mice infected with JEV. Mice lacking α/β-T cells (TCRβ-null) are highly susceptible and die over 10-18 day period as compared to the wild-type (WT) mi ...[more]

PMID: 28151989

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CD8 T cells protect adult naive mice from JEV-induced morbidity via lytic function.

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CD8 T cells protect adult naive mice from JEV-induced morbidity via lytic function.

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