title: Alteration in frequency and function of CD4⁺CD25⁺FOXP3⁺ regulatory T cells in patients with immune thrombocytopenic purpura.
abstract: Immune thrombocytopenic purpura (ITP) is an autoimmune bleeding disorder characterized by production of auto-antibodies against platelet antigens. It is obvious that regulatory T cells (Tregs) have a major role in controlling immune homeostasis and preventing autoimmunity.To investigate the frequency and functions of Tregs, twenty ITP patients and twenty age- and sex-matched healthy controls were recruited. The peripheral blood mononuclear cells were isolated and the proportion of Tregs was defined by flow cytometry method. The expression of immune-regulatory markers, cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) and glucocorticoid induced tumor necrosis factor receptor (GITR) were also assessed by quantitative Real-time PCR TaqMan method. For evaluation of Treg function, Tregs were enriched and their ability to inhibit proliferation of T cells was measured and levels of immune-regulatory cytokines IL-10 and TGF-β were also measured.Results showed that the frequency of Tregs and the mean fluorescence intensity of FOXP3 protein significantly decreased in ITP patients compared to those in healthy controls. In addition, there was a significant reduction in relative expression of both CTLA-4 and GITR mRNA in ITP patients (P=0.02 and P=0.006, respectively). The suppressive function of Tregs also diminished in ITP patients compared to that in controls. Both IL-10 and TGF-β cytokines were produced in lower amounts in ITP patients than controls.It could be concluded that alteration in Treg frequency and functional characteristics might be responsible for loss of self-tolerance and subsequently destructive immune responses observed in ITP patients.
authors: Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. nargess_786@yahoo.com.
authors: Nargess
authors: N
authors: Arandi
authors: Abbas
authors: A
authors: Mirshafiey
authors: Mahmood
authors: M
authors: Jeddi-Tehrani
authors: Mohammadreza
authors: M
authors: Shaghaghi
authors: Bamdad
authors: B
authors: Sadeghi
authors: Hassan
authors: H
authors: Abolhassani
authors: Ramazan Ali
authors: RA
authors: Sharifian
authors: Mohammad Saeid
authors: MS
authors: Rahiminejad
authors: Asghar
authors: A
authors: Aghamohammadi
mesh_terms: D000293:Adolescent; D000328:Adult; D018791:CD4 Lymphocyte Count; D060908:CTLA-4 Antigen / Q000097:blood / Q000276:immunology*; D002648:Child; D005260:Female; D051858:Forkhead Transcription Factors / Q000097:blood / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000097:blood / Q000276:immunology; D008297:Male; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000097:blood / Q000276:immunology* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000097:blood / Q000276:immunology
chemical_list: D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508609:IL10 protein, human; D016212:Transforming Growth Factor beta; D016753:Interleukin-10