Medical Immunology (Russia), 2024, 26(5):891-896

Increased proliferative response of highly differentiated CD57+NKG2C+NK cells expressing NKG2A

During infection with cytomegalovirus (HCMV), the content of so-called adaptive NK cells withthe CD57 +NKG2C+ phenotype increases in the peripheral blood, capable of exhibiting specialized functionalactivity aimed at controlling the infection upon repeated encounter with the antigen. In addition, adaptive NKcells are characterized by antitumor cytotoxic effects and long lifespan. In this regard, HCMV- specific adaptiveNK cells are of interest as a therapeutic agent. The specificity of adaptive NK cells to HCMV is determinedprimarily by the recognition of viral peptides presented by the non-classical class I histocompatibilitymolecule HLA-E, by means of the activating receptor NKG2C. However, being highly differentiated, adaptiveCD57 +NKG2C+ cells tend to proliferate less well in response to soluble stimuli compared to less differentiatedNK cells, making their accumulation in vitro difficult. In addition to the activating receptor NKG2C, adaptiveNK cells express receptors of the KIR family, but mostly do not express the inhibitory receptor NKG2A, whichis also capable of recognizing the HLA-E molecule presenting the HCMV peptide. Despite the fact that, ingeneral, in CD57+NKG2C+NK cells from HCMV- seropositive donors, NKG2A expression is greatly reduced,in a number of individuals a significant proportion of NKG2A-positive cells was observed in this fraction. Usingthe example of an individual with a high proportion of NKG2A+ in the population of CD57+NKG2C+NK cellsand a high titer of antibodies to HCMV, we showed that when stimulated with IL-2 in combination withK562-mbIl21 feeder cells, NK cells of the CD57+NKG2C+NKG2A+ subpopulation exhibit increasedproliferative activity in comparison with CD57 +NKG2C+NKG2A- , and also have a higher level of expressionof the adapter molecule FcεRIγ, taking part in signal transduction of activating receptors NKp30, NKp46and CD16. Thus, NKG2A-positive CD57+NKG2C+ cells may be potential precursors of adaptive NK cellsand mediate their accumulation during HCMV infection. The data obtained in this work allows us to deepenknowledge in the field of differentiation of HCMV - specific NK cells, as well as expand the range of approachesto the accumulation of highly cytotoxic adaptive-like NK cell effectors in vitro.

IBCH: 11544
Ссылка на статью в журнале: https://www.mimmun.ru/mimmun/article/view/3086
Кол-во цитирований на 10.2024: 0
Данные статьи проверены модераторами 2024-11-08

Список научных проектов, где отмечена публикация

  1. -Противовирусная роль NK-клеток при инфекциях CMV и SARS-CoV-2 и подходы к использованию противовирусного потенциала NK-клеток в терапии (January 6, 2022 — December 31, 2024). Kovalenko E.I.. Grant, RSF.