BackgroundB7 costimulatory molecules are expressed on antigen presenting cells (APCs) and are important regulators of T cell activation. We investigated the role of the B7 family of costimulatory molecules in the development of the systemic maternal immune tolerance during healthy pregnancy (HP). We also aimed to investigate the intracellular expression of indoleamine-2,3-dioxygenase (IDO) and plasma levels of tryptophane (TRP), kynurenine (KYN) and kynurenic acid (KYNA), important molecules with immunoregulatory properties, in order to describe their potential contribution to the pregnancy-specific maternal immune tolerance.MethodsWe determined the frequency of activated (CD11b+) monocytes expressing B7-1, B7-2, B7-H1, and B7-H2, and that of T cells and CD4+ T helper cells expressing CD28, CTLA-4, PD-1, and ICOS in peripheral blood samples of healthy pregnant (HP) and non-pregnant (NP) women using flow cytometry. We also examined the intracellular expression of IDO applying flow cytometry and plasma levels of TRP, KYN and KYNA using high-performance liquid chromatography.ResultsA significant increase in the prevalence of CD28+ T cells was observed in HP compared to NP women. At the same time a decrease was shown in the expression of CTLA-4 on these cells. The frequency of CD80+ monocytes was lower in HP women. The prevalence of IDO-expressing T cells and monocytes was higher in HP compared to NP women. Plasma KYN, KYNA and TRP levels were lower, while at the same time, the KYN/TRP ratio was higher in HP than in NP women.ConclusionsCostimulation via CD28 may not contribute to the immunosuppressive environment, at least in the third trimester of pregnancy. The development of the pregnancy-specific immune tolerance in the mechanism of B7 costimulation may be more related to the altered expression of B7 proteins on APCs rather than that of their receptors on T cells. The elevated intracellular IDO expression in monocytes and T cells, as well as higher plasma enzymatic IDO activity are likely to contribute to the systemic immunosuppressive environment in the third trimester characteristic for healthy gestation.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2393-14-306) contains supplementary material, which is available to authorized users.

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a b s t r a c tAlterations in the expression of B7 costimulatory molecules and their receptors, as well as differences in the tryptophan (TRP) catabolic pathway, may influence immunological reactivity of umbilical cord blood (UCB) compared with adult peripheral blood (APB) T lymphocytes. We determined the frequency of activated (CD11b þ ) monocytes expressing B7-1, B7-2, B7-H1, and B7-H2, and that of T cells and CD4 þ T helper cells expressing CD28, cytotoxic T lymphocyte antigen 4 (CTLA-4), programmed death-1 receptor, and inducible costimulator of T cells in UCB and APB samples using flow cytometry. We also examined the intracellular expression of indoleamine 2,3-dioxygenase (IDO) applying flow cytometry and plasma levels of TRP, kynurenine (KYN), and kynurenic acid using high-performance liquid chromatography. The level of CTLA-4 expression on CD4 cells was higher in UCB compared with in APB, indicating that the possibility of CD28-mediated costimulation may be decreased. The level of the corresponding costimulator molecule, B7-2, was also elevated. Therefore, this inhibitory relation may function to a higher extent in UCB than in APB. The plasma KYN to TRP (K/T) ratio was 2-fold higher in UCB compared with APB. However, the capacity of UCB monocytes to produce IDO compared with APB monocytes was lower, and reverse signaling via B7-2 in UCB monocytes was found to be immature, which suggests that the observed increase in K/T ratio may be due to placental, rather than fetal, overexpression of IDO in competent cells. These factors may all contribute to the previously observed reduced reactivity of UCB T lymphocytes compared to APB T cells.

The efficiency of the immune response is well-known to be decreased in the perinatal period compared to adulthood. Several factors may play a role in this finding, including immaturity of adaptive immune responses, as well as alterations in the prevalence and functionality in elements of humoral and cellular immune reactions compared to adult-type immunity. The process of antigen presentation and adequate T cell function are cornerstone features in coordinating the immune response already at this early age. Over the recent decades, several studies have revealed remarkable details that contribute to these alterations. However, many aspects of the exact mechanisms are still not fully understood. In this review, we aim to summarize current knowledge of studies of altered cell prevalence and functionality that contribute to differences of antigen presentation and the T cell immune response between the perinatal and adult periods. Decreased level of antigen presentation, lower expression of costimulatory molecules, lower Th1 and Th17 response, and deficient function of regulatory elements are the most important differences in CB compared with adult peripheral blood. These differences are of practical importance from two distinct aspects. First, the decreased efficiency of the immune response plays an important role in the development of several diseases affecting preterm and term neonates, as well as in a higher incidence of infections compared to adults. Second, umbilical cord blood (UCB)-derived hematopoietic stem cells are widely used in the treatment of different hematological and immunological disorders. The prevalence of graft-versus-host disease (GVHD) is lower upon UCB-derived stem cell transplantation compared to adult peripheral blood or bone marrow-derived stem cells. Therefore, the deeper understanding of the mechanisms contributing to a decreased T cell response is of importance in improving therapeutic efficiency in related disorders.