Activation status dictates the function of unlicensed natural killer cells in mice and humans. Blood Adv 2021 Oct 26;5(20):4219-4232
Date
09/09/2021Pubmed ID
34496010Pubmed Central ID
PMC8945636DOI
10.1182/bloodadvances.2021004589Scopus ID
2-s2.0-85118595142 (requires institutional sign-in at Scopus site) 1 CitationAbstract
Natural killer (NK) cells are involved in innate defense against viral infection and cancer. NK cells can be divided into subsets based on the ability of different receptors to bind to major histocompatibility (MHC) class 1 molecules, resulting in differential responses upon activation in a process called "licensing" or "arming." NK cells expressing receptors that bind self-MHC are considered licensed due to an augmented effector lytic function capability compared with unlicensed subsets. However, we demonstrated that unlicensed NK subsets instead positively regulate the adaptive T-cell response during viral infections that are related to localization and cytokine production. In this study, the differential effects of the two types of NK subsets were contingent on the environment in viral infection and hematopoietic stem cell transplantation (HSCT) models. Infection of mice with high-dose (HD) murine cytomegalovirus (MCMC) led to a loss of licensing-associated differences, as compared with mice with low-dose (LD) infection: the unlicensed NK subset no longer localized in lymph nodes (LNs), but instead remained at the site of infection. Similarly, the patterns observed during HD infection paralleled the phenotypes of both human and mouse NK cells in an HSCT setting where NK cells exhibit an activated phenotype. However, in contrast to the effects of subset depletion in T-cell replete models, the licensed NK cell subsets still dominated antiviral responses after HSCT. Overall, our results highlight the intricate tuning of NK cells and how it affects overall immune responses with regard to licensing patterns and their dependency on the level of stimulation and activation status.
Author List
Aguilar EG, Dunai C, Judge SJ, Zamora AE, Khuat LT, Vick LV, Collins CP, Stoffel KM, Alvarez M, Barao I, Miller JS, Blazar BR, Chevallier P, Retiere C, Canter RJ, Murphy WJAuthor
Anthony E. Zamora PhD Assistant Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsHematopoietic Stem Cell Transplantation
Humans
Killer Cells, Natural
Mice
Mice, Inbred C57BL
Muromegalovirus
