title: B7 costimulation and intracellular indoleamine-2,3-dioxygenase (IDO) expression in peripheral blood of healthy pregnant and non-pregnant women.
abstract: 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.
authors.forename: Enikő
authors.initials: E
authors.lastname: Grozdics
authors.forename: László
authors.initials: L
authors.lastname: Berta
authors.forename: Anna
authors.initials: A
authors.lastname: Bajnok
authors.forename: Gábor
authors.initials: G
authors.lastname: Veres
authors.forename: István
authors.initials: I
authors.lastname: Ilisz
authors.forename: Péter
authors.initials: P
authors.lastname: Klivényi
authors.forename: János
authors.initials: J
authors.lastname: Rigó
authors.forename: László
authors.initials: L
authors.lastname: Vécsei
authors.forename: Tivadar
authors.initials: T
authors.lastname: Tulassay
authors.affiliation: First Department of Pediatrics, Semmelweis University, Bókay u, 53-54, Budapest H-1083, Hungary. toldigergely@yahoo.com.
authors.forename: Gergely
authors.initials: G
authors.lastname: Toldi
mesh_terms: D000328:Adult; D060887:B7 Antigens / Q000032:analysis*; D018106:CD28 Antigens / Q000032:analysis; D018791:CD4 Lymphocyte Count; D060908:CTLA-4 Antigen / Q000032:analysis; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology*; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000032:analysis*; D007736:Kynurenic Acid / Q000097:blood; D007737:Kynurenine / Q000097:blood; D009000:Monocytes / Q000737:chemistry*; D011247:Pregnancy / Q000276:immunology*; D061026:Programmed Cell Death 1 Receptor / Q000032:analysis; D013601:T-Lymphocytes / Q000737:chemistry*; D014364:Tryptophan / Q000097:blood
chemical_list: D060887:B7 Antigens; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D007737:Kynurenine; D014364:Tryptophan; D007736:Kynurenic Acid