CD8 T cells protect adult naive mice from JEV-induced morbidity via lytic function.
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 th...
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ftdoajarticles:oai:doaj.org/article:e1f7020cca26447fbab78d1981c63aeb 2023-05-15T15:13:47+02:00 CD8 T cells protect adult naive mice from JEV-induced morbidity via lytic function. Nidhi Jain Neelam Oswal Amanpreet Singh Chawla Tanvi Agrawal Moanaro Biswas Sudhanshu Vrati Satyajit Rath Anna George Vineeta Bal Guruprasad R Medigeshi 2017-02-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0005329 https://doaj.org/article/e1f7020cca26447fbab78d1981c63aeb EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC5308832?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0005329 https://doaj.org/article/e1f7020cca26447fbab78d1981c63aeb PLoS Neglected Tropical Diseases, Vol 11, Iss 2, p e0005329 (2017) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2017 ftdoajarticles https://doi.org/10.1371/journal.pntd.0005329 2022-12-31T16:22:28Z 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) 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 TCRβ-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 TCRβ-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 γ/δ-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. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 11 2 e0005329 |
institution |
Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Nidhi Jain Neelam Oswal Amanpreet Singh Chawla Tanvi Agrawal Moanaro Biswas Sudhanshu Vrati Satyajit Rath Anna George Vineeta Bal Guruprasad R Medigeshi CD8 T cells protect adult naive mice from JEV-induced morbidity via lytic function. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
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) 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 TCRβ-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 TCRβ-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 γ/δ-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. |
format |
Article in Journal/Newspaper |
author |
Nidhi Jain Neelam Oswal Amanpreet Singh Chawla Tanvi Agrawal Moanaro Biswas Sudhanshu Vrati Satyajit Rath Anna George Vineeta Bal Guruprasad R Medigeshi |
author_facet |
Nidhi Jain Neelam Oswal Amanpreet Singh Chawla Tanvi Agrawal Moanaro Biswas Sudhanshu Vrati Satyajit Rath Anna George Vineeta Bal Guruprasad R Medigeshi |
author_sort |
Nidhi Jain |
title |
CD8 T cells protect adult naive mice from JEV-induced morbidity via lytic function. |
title_short |
CD8 T cells protect adult naive mice from JEV-induced morbidity via lytic function. |
title_full |
CD8 T cells protect adult naive mice from JEV-induced morbidity via lytic function. |
title_fullStr |
CD8 T cells protect adult naive mice from JEV-induced morbidity via lytic function. |
title_full_unstemmed |
CD8 T cells protect adult naive mice from JEV-induced morbidity via lytic function. |
title_sort |
cd8 t cells protect adult naive mice from jev-induced morbidity via lytic function. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2017 |
url |
https://doi.org/10.1371/journal.pntd.0005329 https://doaj.org/article/e1f7020cca26447fbab78d1981c63aeb |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 11, Iss 2, p e0005329 (2017) |
op_relation |
http://europepmc.org/articles/PMC5308832?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0005329 https://doaj.org/article/e1f7020cca26447fbab78d1981c63aeb |
op_doi |
https://doi.org/10.1371/journal.pntd.0005329 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
11 |
container_issue |
2 |
container_start_page |
e0005329 |
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1766344313548046336 |