title: Functional role of CD4+CD25+ regulatory T cells and transforming growth factor-beta1 in childhood immune thrombocytopenic purpura.
abstract: CD4+CD25+ regulatory T cells (Tregs) are critical in maintaining self tolerance and preventing organ specific autoimmune diseases. Their role in childhood immune thrombocytopenic purpura (ITP), an immune disorder in which the production of platelet autoantibodies might be caused by cytokine network dysregulation, has not been clearly defined. Transforming Growth Factor-beta1 (TGF-beta1) has been suggested to mediate Tregs suppressive function. The aim of this study was to assess cell populations of CD4+CD25+ T regulatory cells as well as mRNA expression of TGF-beta1 level in peripheral blood of children with ITP and evaluate their possible role in prediction of disease severity and response to therapy. Thirty-three children with ITP (13 acute and 20 chronic cases) and 10 healthy controls were studied. CD4+CD25+ regulatory T cells were assessed in peripheral blood by flowcytometry. Expression of TGF-beta1 mRNA was examined by real-time quantitative polymerase chain reaction assay. The frequency of CD4+CD25+ Tregs was significantly decreased in acute and chronic ITP patients as compared to controls. Acute ITP patients had significantly lower percentage of Tregs compared with chronic ITP patients. Higher frequency of CD4+CD25+ Tregs was detected in chronic ITP patients with platelet count >100 x 10(9)/L compared with patients with platelet count <100 x 10(9)/L and in steroid responsive patients compared with steroid resistant patients. The expression of mRNA TGF-beta1 level was significantly lower in acute and chronic ITP patients compared with controls and in chronic ITP patients with pltc <100 x 10(9)/L in comparison with patients with pltc > 100 x l0(9)/L. A significant positive correlation was found between percentage of CD4+CD25+ Tregs and mRNA expression of TGF-beta1 in chronic ITP patients. In conclusion, immune regulation of TGF-beta1 by Tregs may play a fundamental role in the pathogenesis of childhood immune thrombocytopenic purpura. This might form a base for future specific immunomodulatory therapies for ITP.
authors.affiliation: Department of Microbiology & Immunology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
authors.forename: Nehal M A
authors.initials: NM
authors.lastname: Fahim
authors.forename: Eman
authors.initials: E
authors.lastname: Monir
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D001323:Autoantibodies / Q000276:immunology; D001792:Blood Platelets / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D005260:Female; D006801:Humans; D008297:Male; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D001323:Autoantibodies; D053773:Transforming Growth Factor beta1