Journal
VIROLOGY
Volume 519, Issue -, Pages 131-144Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2018.04.012
Keywords
NK cells; CD4 T cells; LCMV; Vaccinia virus; NKG2A; Interferon; IRF4
Categories
Funding
- Ellison Medical Foundation New Scholar Award
- United States National Institutes of Health (NIH) [DA038017]
- NIH [AI109858]
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Natural killer (NK) cells control antiviral adaptive immune responses in mice during some virus infections, but the universality of this phenomenon remains unknown. Lymphocytic choriomeningitis virus (LCMV) infection of mice triggered potent cytotoxic activity of NK cells (NKLCMV) against activated CD4 T cells, tumor cells, and allogeneic lymphocytes. In contrast, NK cells activated by vaccinia virus (VACV) infection (NKVACV) exhibited weaker cytolytic activity against each of these target cells. Relative to NKLCMV cells, NKVACV cells exhibited a more immature (CD11b CD27(+)) phenotype, and lower expression levels of the activation marker CD69, cytotoxic effector molecules (perforin, granzyme B), and the transcription factor IRF4. NKVACV cells expressed higher levels of the inhibitory molecule NKG2A than NKLCMV cells. Consistent with this apparent lethargy, NKVACV cells only weakly constrained VACV-specific CD4 T-cell responses. This suggests that NK cell regulation of adaptive immunity, while universal, may be limited with viruses that poorly activate NK cells.
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