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Publication : CD8<sup>+</sup> T cells are crucial for humoral immunity establishment by SA14-14-2 live attenuated Japanese encephalitis vaccine in mice.

First Author  Kalia A Year  2021
Journal  Eur J Immunol Volume  51
Issue  2 Pages  368-379
PubMed ID  32749679 Mgi Jnum  J:302288
Mgi Id  MGI:6506954 Doi  10.1002/eji.202048745
Citation  Kalia A, et al. (2021) CD8(+) T cells are crucial for humoral immunity establishment by SA14-14-2 live attenuated Japanese encephalitis vaccine in mice. Eur J Immunol 51(2):368-379
abstractText  The live attenuated SA14-14-2 Japanese encephalitis (JE) vaccine is a historical vaccine that protects against JE. Despite its extensive use, the mechanism of protective immunity conferred by the SA14-14-2 vaccine is not well established. Here, we used mouse models to understand the mechanism of the development of humoral immunity against the vaccine. The vaccine induces robust GC responses within a week postimmunization. In lethal virus challenge, we show that CD4(+) T cells alone, but not CD8(+) T cells, are sufficient to confer vaccine-mediated protection. However, the CD4-mediated protection was potentiated in the presence of vaccine-primed CD8(+) T cells. Employing CD8-deficient mice, we show that both the protective traits of CD4(+) T cells and the quality of antibody response to the vaccine are impaired in absence of CD8(+) T cells. We further demonstrate that the poor protective immune response induced by the vaccine in absence of CD8(+) T cells is mainly due to the impaired differentiation and function of follicular Th cells, leading to suboptimal GC reaction. Our study highlights an unprecedented role of CD8(+) T cells in the establishment of humoral responses to the vaccine. By elucidating underlying cellular determinants of vaccine-induced protective immunity, our work has implications for rational design of vaccines against JE virus and related flaviviruses.
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