B7 costimulation and intracellular indoleamine-2,3-dioxygenase (IDO) expression in peripheral blood of healthy pregnant and non-pregnant women

BMC Pregnancy and Childbirth

Gergely Toldi⁵  Tivadar Tulassay⁵  László Vécsei²  János Rigó⁶  Péter Klivényi¹  István Ilisz³  Gábor Veres¹  Anna Bajnok⁴  László Berta⁴  Enikő Grozdics⁴ 

[1] Department of Neurology, Faculty of Medicine, Albert Szent-Györgyi Clinical Center, University of Szeged, Semmelweis u. 6, Szeged H-6725, Hungary;MTA-SZTE Neuroscience Research Group, Semmelweis u. 6, Szeged H-6725, Hungary;Department of Inorganic and Analytical Chemistry, University of Szeged, Dóm tér 7, H-6720 Szeged, Hungary;First Department of Pediatrics, Semmelweis University, Bókay u. 53-54, Budapest H-1083, Hungary;MTA-SE Pediatrics and Nephrology Research Group, Bókay u. 53-54, Budapest H-1083, Hungary;First Department of Obstetrics and Gynecology, Semmelweis University, Baross u. 27, Budapest H-1088, Hungary

关键词: Tryptophan;    T cell;    Monocyte;    Kynurenine;    Indoleamine 2,3-dioxygenase;    CTLA-4;    CD28;    B7;   

Others  :  1125528
DOI  :  10.1186/1471-2393-14-306

 received in 2014-05-07, accepted in 2014-09-02,  发布年份 2014

【 摘 要 】

Background

B7 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.

Methods

We 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.

Results

A 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.

Conclusions

Costimulation 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.

【 授权许可】

   
2014 Grozdics et al.; licensee BioMed Central Ltd.

【 图 表 】

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