title: Immunoregulatory molecules in patients with gestational diabetes mellitus.
abstract: Induction of maternal-fetal immune tolerance is essential for the development of normal pregnancy. Impaired expression of costimulatory molecules may lead to intense inflammatory reaction, a mechanism involved in the pathophysiology of gestational diabetes mellitus (GDM). The aim of this study was to investigate whether immunoregulatory molecules are involved in the physiopathology of GDM. This case-control study included 30 healthy pregnant women and 20 GDM patients. Flow cytometry was used to assess peripheral blood T subpopulations (CD4(+) and CD8(+)), the expression of immunoregulatory molecules (CD28, ICOS, CTLA-4, and PD-1) and activation markers (CD69 and HLA-DR). Compared to healthy women, GDM patients had a significantly higher frequency of CD4(+)CD69(+) and CD8(+)CD69(+) T cells; only patients with insulin-treated GDM had increased numbers of CD4(+)HLA-DR(+) T cells. We also observed significantly higher percentages of CD4(+)CD28(+)HLA-DR(+), CD3(+)CD4(+)ICOS(+), CD3(+)CD4(+)PD-1(+), CD8(+)CD28(+)CD69(+), CD8(+)CD28(+)HLA-DR(+), CD8(+)CTLA-4(+)HLA-DR(+), and CD3(+)CD8(+)ICOS(+) T cells and lower frequency of CD3(+)CD4(+)CTLA-4(+), CD3(+)CD8(+)CTLA-4(+), and CD8(+)ICOS(+)HLA-DR(+) T cells in GDM patients compared to healthy pregnant women. This first study assessing costimulatory molecules in GDM patients shows that these patients have exacerbated markers of T cell activation along with CTLA-4 deficiency, findings that indicate that the maternal-fetal tolerance is compromised in these patients.
authors.affiliation: Department of Obstetrics, Universidade Federal de São Paulo, Rua Pedro de Toledo 669, 9 Andar, São Paulo, SP, 04939 032, Brazil.
authors.forename: Karen Priscilla Tezotto
authors.initials: KP
authors.lastname: Pendeloski
authors.forename: Rosiane
authors.initials: R
authors.lastname: Mattar
authors.forename: Maria Regina
authors.initials: MR
authors.lastname: Torloni
authors.forename: Caio Perez
authors.initials: CP
authors.lastname: Gomes
authors.forename: Sandra Maria
authors.initials: SM
authors.lastname: Alexandre
authors.forename: Silvia
authors.initials: S
authors.lastname: Daher
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000097:blood; D000945:Antigens, Differentiation, T-Lymphocyte / Q000097:blood*; D018106:CD28 Antigens / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D060908:CTLA-4 Antigen / Q000097:blood; D016022:Case-Control Studies; D061025:Costimulatory and Inhibitory T-Cell Receptors / Q000097:blood*; D016640:Diabetes, Gestational / Q000097:blood*; D005260:Female; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000097:blood; D006801:Humans; D060889:Inducible T-Cell Co-Stimulator Protein / Q000097:blood; D037181:Lectins, C-Type / Q000097:blood; D008875:Middle Aged; D011247:Pregnancy; D061026:Programmed Cell Death 1 Receptor / Q000097:blood; D055815:Young Adult; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; D061025:Costimulatory and Inhibitory T-Cell Receptors; D006684:HLA-DR Antigens; D060889:Inducible T-Cell Co-Stimulator Protein; D037181:Lectins, C-Type; D061026:Programmed Cell Death 1 Receptor; D000099192:CD69 Antigens; C556692:ICOS protein, human; C105992:PDCD1 protein, human