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

Autor: N. A. Alekseeva, Yu. D. Vavilova, E. I. Kovalenko
Jazyk: ruština
Rok vydání: 2024
Předmět:
Zdroj: Медицинская иммунология, Vol 26, Iss 5, Pp 891-896 (2024)
Druh dokumentu: article
ISSN: 1563-0625
2313-741X
DOI: 10.15789/1563-0625-IPR-16778
Popis: During infection with cytomegalovirus (HCMV), the content of so-called adaptive NK cells with the CD57+NKG2C+ phenotype increases in the peripheral blood, capable of exhibiting specialized functional activity aimed at controlling the infection upon repeated encounter with the antigen. In addition, adaptive NK cells are characterized by antitumor cytotoxic effects and long lifespan. In this regard, HCMV-specific adaptive NK cells are of interest as a therapeutic agent. The specificity of adaptive NK cells to HCMV is determined primarily by the recognition of viral peptides presented by the non-classical class I histocompatibility molecule HLA-E, by means of the activating receptor NKG2C. However, being highly differentiated, adaptive CD57+NKG2C+ cells tend to proliferate less well in response to soluble stimuli compared to less differentiated NK cells, making their accumulation in vitro difficult. In addition to the activating receptor NKG2C, adaptive NK cells express receptors of the KIR family, but mostly do not express the inhibitory receptor NKG2A, which is also capable of recognizing the HLA-E molecule presenting the HCMV peptide. Despite the fact that, in general, 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. Using the example of an individual with a high proportion of NKG2A+ in the population of CD57+NKG2C+NK cells and a high titer of antibodies to HCMV, we showed that when stimulated with IL-2 in combination with K562-mbIl21 feeder cells, NK cells of the CD57+NKG2C+NKG2A+ subpopulation exhibit increased proliferative activity in comparison with CD57+NKG2C+NKG2A-, and also have a higher level of expression of the adapter molecule FcεRIγ, taking part in signal transduction of activating receptors NKp30, NKp46 and CD16. Thus, NKG2A-positive CD57+NKG2C+ cells may be potential precursors of adaptive NK cells and mediate their accumulation during HCMV infection. The data obtained in this work allows us to deepen knowledge in the field of differentiation of HCMV-specific NK cells, as well as expand the range of approaches to the accumulation of highly cytotoxic adaptive-like NK cell effectors in vitro.
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