Expression of inhibitory receptors PD-1, CTLA-4, and Tim-3 by peripheral T cells during pregnancy

Background. Inhibitory receptors and their ligands (also called checkpoint molecules) are important feedback regulators of the immune response. However, their role in immunological adaptation during pregnancy remains poorly understood.The aim of the study was to evaluate the level of checkpoint mole...

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Main Authors: E. A. Smetanenko, N. A. Khonina, O. Yu. Leplina, M. A. Tikhonova, E. V. Batorov, N. M. Pasman, E. R. Chernykh
Format: Article
Language:English
Published: Siberian State Medical University (Tomsk) 2022-10-01
Series:Бюллетень сибирской медицины
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Online Access:https://bulletin.ssmu.ru/jour/article/view/4911
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author E. A. Smetanenko
N. A. Khonina
O. Yu. Leplina
M. A. Tikhonova
E. V. Batorov
N. M. Pasman
E. R. Chernykh
author_facet E. A. Smetanenko
N. A. Khonina
O. Yu. Leplina
M. A. Tikhonova
E. V. Batorov
N. M. Pasman
E. R. Chernykh
author_sort E. A. Smetanenko
collection DOAJ
description Background. Inhibitory receptors and their ligands (also called checkpoint molecules) are important feedback regulators of the immune response. However, their role in immunological adaptation during pregnancy remains poorly understood.The aim of the study was to evaluate the level of checkpoint molecule (PD-1, CTLA-4, Tim-3) expression in peripheral T cells in pregnant women compared with fertile non-pregnant women.Materials and methods. The study included 36 women in the second half of pregnancy without pregnancy complications, 12 of whom had extragenital pathology. The control group consisted of 28 age-matched fertile non-pregnant women. The proportion of CD8+PD-1+, CD8+TIM-3+, CD8+PD-1+TIM-3+, CD4+PD-1+, CD4+TIM-3+, and CD4+PD-1+TIM-3+ was evaluated by flow cytometry using the corresponding monoclonal antibodies (BD Biosciences, USA).Results. The proportion of CD4+Tim-3+ and CD8+PD-1+ Т cells and CD4+ and CD8+ Т lymphocytes co-expressing PD-1 and Tim-3 in the peripheral blood of pregnant women was statistically significantly higher than in non-pregnant women. An increase in CD4+Tim-3+ and CD8+PD-1+ T cells was observed both in pregnant women with and without extragenital pathology. However, pregnant women with extragenital pathology were characterized by a higher CD8+PD-1+ count and a smaller number of CD8+Tim-3+ cells, as well as by a lack of an increase in PD-1+Tim-3+ T cells typical of pregnant women. The number of comorbidities was directly correlated with the proportion of CD8+PD-1+ lymphocytes and inversely correlated with the proportion of CD8+Tim-3+ and CD4+ PD-1+Tim-3+ cells. In addition, the expression of checkpoint molecules was associated with gestational age (a direct correlation was found with the proportion of CD8+Tim-3+, CD4+PD-1+Tim-3+, and CD8+PD-1+Tim-3+ cells) and to a lesser extent – with the age of pregnant women (an inverse relationship was found with the proportion of CD8+Tim-3+ cells).Conclusion. Pregnant women in the second half of pregnancy are characterized by increased expression of PD-1 and Tim-3 molecules in peripheral T cells. At the same time, concomitant extragenital pathology affects the expression of these molecules.
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spelling doaj-art-2fd2ceed56d547aba059e7aff33b8fa62025-08-20T04:00:10ZengSiberian State Medical University (Tomsk)Бюллетень сибирской медицины1682-03631819-36842022-10-01213879510.20538/1682-0363-2022-3-87-952921Expression of inhibitory receptors PD-1, CTLA-4, and Tim-3 by peripheral T cells during pregnancyE. A. Smetanenko0N. A. Khonina1O. Yu. Leplina2M. A. Tikhonova3E. V. Batorov4N. M. Pasman5E. R. Chernykh6Research Institute of Fundamental and Clinical ImmunologyResearch Institute of Fundamental and Clinical Immunology; Institute of Medicine and Psychology, Novosibirsk National Research State UniversityResearch Institute of Fundamental and Clinical ImmunologyResearch Institute of Fundamental and Clinical ImmunologyResearch Institute of Fundamental and Clinical ImmunologyInstitute of Medicine and Psychology, Novosibirsk National Research State UniversityResearch Institute of Fundamental and Clinical ImmunologyBackground. Inhibitory receptors and their ligands (also called checkpoint molecules) are important feedback regulators of the immune response. However, their role in immunological adaptation during pregnancy remains poorly understood.The aim of the study was to evaluate the level of checkpoint molecule (PD-1, CTLA-4, Tim-3) expression in peripheral T cells in pregnant women compared with fertile non-pregnant women.Materials and methods. The study included 36 women in the second half of pregnancy without pregnancy complications, 12 of whom had extragenital pathology. The control group consisted of 28 age-matched fertile non-pregnant women. The proportion of CD8+PD-1+, CD8+TIM-3+, CD8+PD-1+TIM-3+, CD4+PD-1+, CD4+TIM-3+, and CD4+PD-1+TIM-3+ was evaluated by flow cytometry using the corresponding monoclonal antibodies (BD Biosciences, USA).Results. The proportion of CD4+Tim-3+ and CD8+PD-1+ Т cells and CD4+ and CD8+ Т lymphocytes co-expressing PD-1 and Tim-3 in the peripheral blood of pregnant women was statistically significantly higher than in non-pregnant women. An increase in CD4+Tim-3+ and CD8+PD-1+ T cells was observed both in pregnant women with and without extragenital pathology. However, pregnant women with extragenital pathology were characterized by a higher CD8+PD-1+ count and a smaller number of CD8+Tim-3+ cells, as well as by a lack of an increase in PD-1+Tim-3+ T cells typical of pregnant women. The number of comorbidities was directly correlated with the proportion of CD8+PD-1+ lymphocytes and inversely correlated with the proportion of CD8+Tim-3+ and CD4+ PD-1+Tim-3+ cells. In addition, the expression of checkpoint molecules was associated with gestational age (a direct correlation was found with the proportion of CD8+Tim-3+, CD4+PD-1+Tim-3+, and CD8+PD-1+Tim-3+ cells) and to a lesser extent – with the age of pregnant women (an inverse relationship was found with the proportion of CD8+Tim-3+ cells).Conclusion. Pregnant women in the second half of pregnancy are characterized by increased expression of PD-1 and Tim-3 molecules in peripheral T cells. At the same time, concomitant extragenital pathology affects the expression of these molecules.https://bulletin.ssmu.ru/jour/article/view/4911t cellspregnancyinhibitory pd-1tim-3ctla-4 checkpoint molecules
spellingShingle E. A. Smetanenko
N. A. Khonina
O. Yu. Leplina
M. A. Tikhonova
E. V. Batorov
N. M. Pasman
E. R. Chernykh
Expression of inhibitory receptors PD-1, CTLA-4, and Tim-3 by peripheral T cells during pregnancy
Бюллетень сибирской медицины
t cells
pregnancy
inhibitory pd-1
tim-3
ctla-4 checkpoint molecules
title Expression of inhibitory receptors PD-1, CTLA-4, and Tim-3 by peripheral T cells during pregnancy
title_full Expression of inhibitory receptors PD-1, CTLA-4, and Tim-3 by peripheral T cells during pregnancy
title_fullStr Expression of inhibitory receptors PD-1, CTLA-4, and Tim-3 by peripheral T cells during pregnancy
title_full_unstemmed Expression of inhibitory receptors PD-1, CTLA-4, and Tim-3 by peripheral T cells during pregnancy
title_short Expression of inhibitory receptors PD-1, CTLA-4, and Tim-3 by peripheral T cells during pregnancy
title_sort expression of inhibitory receptors pd 1 ctla 4 and tim 3 by peripheral t cells during pregnancy
topic t cells
pregnancy
inhibitory pd-1
tim-3
ctla-4 checkpoint molecules
url https://bulletin.ssmu.ru/jour/article/view/4911
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AT oyuleplina expressionofinhibitoryreceptorspd1ctla4andtim3byperipheraltcellsduringpregnancy
AT matikhonova expressionofinhibitoryreceptorspd1ctla4andtim3byperipheraltcellsduringpregnancy
AT evbatorov expressionofinhibitoryreceptorspd1ctla4andtim3byperipheraltcellsduringpregnancy
AT nmpasman expressionofinhibitoryreceptorspd1ctla4andtim3byperipheraltcellsduringpregnancy
AT erchernykh expressionofinhibitoryreceptorspd1ctla4andtim3byperipheraltcellsduringpregnancy