ORIGINAL RESEARCH

Regulatory T cells and T helper 17 cells expressing CD39 and CD73 ectonucleotidase in children with severe injury

Zakirov RSh1,2, Kuptsova DG1, Freidlin EV1, Semikina EL1, Petrichuk SV1, Karaseva OV1,2
About authors

1 National Medical Research Center for Children's Health, Moscow, Russia

2 Institute of Urgent Children Surgery and Traumatology, Moscow, Russia

Correspondence should be addressed: Rustam Shakirovich Zakirov
Lomonosovsky prospect, 2/1, Moscow, 119296, Russia; ur.dzcn@hsr.vorikaz

About paper

Funding: the study was supported under the State Assignment by the Ministry of Health of Russia, #AAAA–A19–119021190051–6, #122040800163–9

Acknowledgments: the authors express their gratitude to all patients who participated in the study, as well as to colleagues from the department of concomitant injury, anesthesiology and resuscitation of the Research Institute of Emergency Pediatric Surgery and Traumatology of the Moscow Department of Health for their cooperation.

Author contribution: Zakirov RSh, Karaseva OV, Petrichuk SV — study planning, analysis of literature, collection of experimental data, analysis and interpretation of the results, manuscript authoring and editing; Semikina EL — study planning; Kuptsova DG, Freidlin EV — collection of experimental data.

Compliance with the ethical standards: the study was approved by the Ethics Committee of the Institute of Urgent Children Surgery and Traumatology of the Department of Health of Moscow (Minutes #2 of May 26, 2020). Parents of all participants of the study have signed the informed consent form in accordance with the principles of the Declaration of Helsinki.

Received: 2022-11-21 Accepted: 2022-12-11 Published online: 2022-12-24
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Frequent resulting disability and case mortality support the urgency of investigation of the immune response mechanisms triggered by severe injury (SI) in children. This study aimed to determine the informative immunological criteria of traumatic injury severity and prognosis in children (n = 43) based on the assessment of expression of CD39 and CD73 ectonucleotidase in populations of regulatory T cells (Treg, CD4+CD127lowCD25high) and T-helper 17 cells (Th17, CD4+CD161+CD3+) in SI cases grouped by the outcome (favorable (SIfav, n = 24), unfavorable (SIunfav, n = 17) and lethal (n = 2)). With the help of flow cytometry, we identified a pronounced decrease in the absolute number of Treg and Th17, as well as Treg and Th17 expressing CD39 and CD73, in the early post-traumatic period. In the SIfav and SIunfav groups the relative number of Treg and Th17 cells expressing CD39 differed significantly (p <0.05); it was substantially higher form the first to the third day post injury in the SIunfav group. The level of Treg CD39 (44.4%) is a premise for an unfavorable outcome in children surviving an SI. In fatality cases, we registered extremely low ectonucleotidase expression rates: CD39+Treg — 9.52% (9.52–13.75) and CD39+Th17 — 0.92% (0.74–1.1). In the SIunfav group, the intensity of fluorescence (FL) of CD39 on Treg cells in the early post-traumatic period was higher than seen in the SIfav group. The threshold value for the average fluorescence intensity (FL) of CD39 on Treg was 8.25 c.u. In fatality cases, the Treg CD39 FL values were extremely low: 3.95 c.u. (3.7–4.67). The results of the study indicate that in children, the expression of CD39 and CD73 in Treg and Th17 populations is significantly associated with the severity of injury and outcome of the traumatic disease.

Keywords: children, Treg, Th17, CD39, CD73, severe injury, immune suppression

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