title: Decreased Frequencies of Peripheral Blood CD4+CD25+CD127-Foxp3+ in Patients with Graves' Disease and Graves' Orbitopathy: Enhancing Effect of Insulin Growth Factor-1 on Treg Cells.
abstract: Graves' orbitopathy (GO) is characterized by orbital T cell infiltration. We evaluated the regulatory T (Treg) cell fractions induced with IGF-1 in Graves' disease (GD) with and without GO. Peripheral blood mononuclear cells (PBMCs) were obtained from 13 patients with GD without eye manifestations; 10 patients with active GO; and 12 patients with nodular goiter (NG). All the patients from GD, GO, and NG were subclinical hyperthyroid. We analyzed the expression of Treg cell markers (CD4, CD25, CD127-, Foxp3) on T cells and their ability to respond to IGF-1 stimulation. In patients with GD without GO, we found lowered percentages of CD4+Foxp3+cells, as compared to nodular goiter 1.77 vs. 5.42% (p=0.0276). Similarly, significantly reduced frequencies of CD4+CD25+CD127-Foxp3+and CD4+CD25+CD127-cells were observed in GD patients as compared to nodular goiter patients with hyperthyreosis, (0.7 vs. 1.48%) (p=0.0071) and (14.5 vs. 37.2%) (p=0.0051), respectively. In GO with active GO, only the percentage of CD4+CD25+CD127-cells was found to be decreased versus nodular goiter (9.35 vs. 37.2) (p=0.0275). Stimulation of PBMC derived from GO patients with IGF-1 resulted in significant increase of frequency of both CD4+Foxp3+and CD4+CD25+CD127-Foxp3 cells. Decreased frequencies of peripheral blood CD4+CD25+CD127-Foxp3+in patients with GD and GO could be an useful marker of autoimmune process and perhaps a possible target for future therapies. This is the first study demonstrating Treg-enhancing effects of IGF-1. Thus IGF-1 can be accounted for modulating Treg cell-related action in GO.
authors.affiliation: Department of Medical Pathomorphology, Cathedral of Biostructure, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Pawlowski
authors.affiliation: Department of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Kamil
authors.initials: K
authors.lastname: Grubczak
authors.affiliation: Department of Nuclear Medicine, Medical University of Bialystok, Bialystok, Bialystok, Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Kostecki
authors.affiliation: Department of Paediatric Laboratory Diagnostics, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Ilendo-Poskrobko
authors.affiliation: Department of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Moniuszko
authors.affiliation: Department of Haematology, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Pawlowska
authors.affiliation: Department of General Ophthalmology, Medical University of Lublin, Lublin, Poland.
authors.forename: Robert
authors.initials: R
authors.lastname: Rejdak
authors.affiliation: Department of Medical Pathomorphology, Cathedral of Biostructure, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Reszec
authors.affiliation: Department of Nuclear Medicine, Medical University of Bialystok, Bialystok, Bialystok, Poland.
authors.forename: Janusz
authors.initials: J
authors.lastname: Mysliwiec
mesh_terms: D000368:Aged; D015704:CD4 Antigens / Q000097:blood / Q000276:immunology; D005260:Female; D051858:Forkhead Transcription Factors / Q000097:blood / Q000276:immunology; D049970:Graves Ophthalmopathy / Q000097:blood / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000097:blood / Q000276:immunology; D053699:Interleukin-7 Receptor alpha Subunit / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: D015704:CD4 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D053699:Interleukin-7 Receptor alpha Subunit; D007334:Insulin-Like Growth Factor I