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

Abstract

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.

Keywords

• т-клетки
• беременность
• ингибиторные pd-1
• tim-3
• ctla-4 чек-поинт молекулы