Expression of NKG2D by cytotoxic T lymphocytes as a possible mechanism of hemorrhagic fever with renal syndrome immunopathogenesis

Abstract

Introduction. Hemorrhagic fever with renal syndrome (HFRS) is an acute zoonotic viral infection, widespread in the Russian Federation. The disease is caused by hantaviruses, which have the ability to largely modulate immune response.

Aim – determination of the relationship between the phenotypes of the innate and adaptive immunity lymphocytes with their cytotoxic and immunoregulatory properties in HFRS at different stages and severity.

Material and methods. 65 patients with HFRS of moderate and severe course were under observation. Flow cytofluorimetry of the blood cells was performed during each period of the disease with the determination of the phenotypic characteristics of the innate and adaptive immunity lymphocytes. 15 healthy people made up the comparison group.

Results. It was found that the most informative deviations in the febrile period of HFRS from the indicators in the comparison group are subjected to the dynamics of two categories of cells. Cytotoxic T lymphocytes (CTLs) expressing such activation marker as the C-type lectin receptor NKG2D (CD3+CD8+CD314+), as well as regulatory T cells (Treg) of mainly CD3+CD8+FoxP3+ phenotype. In the oligouric period of HFRS, the predominance of the NKG2D-dependent rather than CD25-dependent activation mechanism in the CTL was noted. In the polyuric period, a significant increase of NKT number was recorded as well as a decrease of T cells number (mainly T helpers) and NKG2D+ NK cells.

Conclusion. The obtained results, in addition to applied value, allow us to propose a hypothesis on the pathogenetic value of the expression of NKG2D receptors by CTLs and the possibility of interrelation of this mechanism with the peculiarities of the processes of reprogramming of the CTL to NKT, the formation of Tregs, the development of immunological memory in HFRS.

Keywords:hemorrhagic fever with renal syndrome; cytotoxic T-lymphocytes; regulatory T-cells; NKG2D-receptor

For citation: Ivanov M.F., Balmasova I.P., Zhestkov A.V., Konstantinov D.Yu., Malova E.S. Expression of NKG2D by cytotoxic T lymphocytes as a possible mechanism of hemorrhagic fever with renal syndrome immunopathogenesis. Immunologiya. 2023; 44 (1): 93–102. DOI: https://doi.org/10.33029/0206-4952-2023-44-1-93-102 (in Russian)

Funding. The study had no sponsor support.

Conflict of interests. The authors declare no conflict of interests.

Authors’ contribution. Concept and design of the study – Ivanov M.F., Balmasova I.P., Zhestkov A.V.; data collection and processing – Ivanov M.F., Konstantinov D.Yu.; statistical data processing – Ivanov M.F.; text writing – Ivanov M.F.; article editing – Balmasova I.P., Malova E.S.

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