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 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.
Immunobiology, National Institute of Immunology, New Delhi, India.
Nidhi
N
Jain
Immunobiology, National Institute of Immunology, New Delhi, India.
Neelam
N
Oswal
Immunobiology, National Institute of Immunology, New Delhi, India.
Amanpreet Singh
AS
Chawla
Vaccine and Infectious Disease Research Centre, Translational Health Science and Technology Institute, Faridabad, India.
Tanvi
T
Agrawal
Immunobiology, National Institute of Immunology, New Delhi, India.
Moanaro
M
Biswas
Vaccine and Infectious Disease Research Centre, Translational Health Science and Technology Institute, Faridabad, India.
Sudhanshu
S
Vrati
Immunobiology, National Institute of Immunology, New Delhi, India.|Vaccine and Infectious Disease Research Centre, Translational Health Science and Technology Institute, Faridabad, India.
Satyajit
S
Rath
Immunobiology, National Institute of Immunology, New Delhi, India.
Anna
A
George
Immunobiology, National Institute of Immunology, New Delhi, India.|Vaccine and Infectious Disease Research Centre, Translational Health Science and Technology Institute, Faridabad, India.
Vineeta
0000-0002-8995-2045
V
Bal
Vaccine and Infectious Disease Research Centre, Translational Health Science and Technology Institute, Faridabad, India.
Guruprasad R
GR
Medigeshi
D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004664:Encephalitis Virus, Japanese / Q000235:genetics / Q000502:physiology*; D004672:Encephalitis, Japanese / Q000276:immunology* / Q000401:mortality* / Q000517:prevention & control / Q000821:virology; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma