Relationship of levels of CD4+CD25+ regulatory T cells and expression of Foxp3 mRNA in peripheral blood with serum immunoglobulin E level in children with bronchiolitis
ZHU Ya-Fei, ZHU Jian-Yang, LI Wei-Wu, LAN Chen-Fu, FANG Jing, LIN Hai-Ling.
Department of Pediatrics, Fifth Affiliated Hospital of Wenzhou Medical College/Lishui Central Hospital, Lishui, Zhejiang 323000, China.
Abstract OBJECTIVE: To study the roles of CD4+CD25+ regulatory T cells and Foxp3 mRNA in peripheral blood as well as serum total immunoglobulin E (IgE) in the pathogenesis of bronchiolitis caused by respiratory syncytial virus (RSV). METHODS: The proportion of CD4+CD25+ regulatory T cells and expression of Foxp3 mRNA in peripheral blood, and total serum IgE level were tested by flow cytometry, RT-PCR and ELISA respectively in 57 children with RSV bronchiolitis (26 atopic patients and 31 nonatopic patients). Twenty five healthy children were used as the control group. RESULTS: The proportion of CD4+CD25+ regulatory T cells in peripheral blood in children with bronchiolitis, either in the atopic (7.7±1.6%)or the nonatopic group (8.8±2.1%), was significantly lower than that in the control group (10.5±1.6%) (P<0.01). Foxp3 mRNA expression in peripheral blood was significantly lower in both atopic and nonatopic children with bronchiolitis than that in the control group (P<0.01). Significantly increased total serum IgE level was noted in both atopic (241.2±102.5 IU/mL) and nonatopic children (125.5±63.2 IU/mL) with bronchiolitis compared with that in the control group (27.2±10.5 IU/ml) (P<0.01). There were significant differences in the proportion of CD4+CD25+ regulatory T cells and Foxp3 mRNA expression in peripheral blood (P<0.05) as well as total serum IgE level (P<0.01) between the atopic and the nonatopic group. The proportion of CD4+CD25+ regulatory T cells (r=-0.70, P<0.01) and Foxp3 mRNA expression in peripheral blood (r=-0.79, P<0.01) were closely negatively correlated to total serum IgE level. CONCLUSIONS: Both the proportion of CD4+CD25+ regulatory T cells and Foxp3 mRNA expression in peripheral blood were reduced, in contrast, the total serum IgE level increased in children with RSV bronchiolitis. This suggested that CD4+CD25+ regulatory T cells and Foxp3 mRNA together with IgE participated in the pathogenesis of RSV bronchiolitis.[Chin J Contemp Pediatr, 2009, 11 (5):349-353]
ZHU Ya-Fei,ZHU Jian-Yang,LI Wei-Wu et al. Relationship of levels of CD4+CD25+ regulatory T cells and expression of Foxp3 mRNA in peripheral blood with serum immunoglobulin E level in children with bronchiolitis[J]. 中国当代儿科杂志, 2009, 11(05): 349-353.
ZHU Ya-Fei,ZHU Jian-Yang,LI Wei-Wu et al. Relationship of levels of CD4+CD25+ regulatory T cells and expression of Foxp3 mRNA in peripheral blood with serum immunoglobulin E level in children with bronchiolitis[J]. CJCP, 2009, 11(05): 349-353.
[1]Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+ CD25+ regulatory T cells[J]. Nat Immunol, 2003, 4(4):330-336.
[3]Hamelmann E, Tadeda K, Oshiba A, Gelfand EW. Role of IgE in the development of allergic airway inflammation and airway hyperresponsiveness—a murine model[J]. Allergy, 1999, 54(4):297-305.
[7]Jaffar Z, Sivakunu T, Roberts K. CD4+CD25+T cells regulate airway eosinophilic inflammation by modulating the Th2 cell phenotype[J]. J Immunol, 2004, 172(6): 3842-3849.
[8]Taylor PA, Noelle RJ, Blazar BR. CD4+CD25+ immune regulatory T cells are required for induction of tolerance to alloantigen via costimulatory blockade[J]. J Exp Med, 2001, 193(11):1311-1318.
[9]Smit JJ, Boon L, Lukacs NW. Respiratory virus-induced regulation of asthma-like responses in mice depends upon CD8 T cells and interferon-gamma production[J]. Am J Pathol, 2007, 171(6):1944-1951.
[10]Romagnani S. Lymphokine production by human T cells in disease states[J]. Annu Rev Immunol, 1994, 12(4):227-257.
[11]Waris ME, Tsou C, Erdman DD, Day DB, Anderson LJ. Priming with live respiratory syncytial virus(RSV) prevents the enhanced pulmonary inflammatory response seen after RSV challenge in BALB/c mice immunized with formalin-inactivated RSV[J]. J Virol, 1997, 71(9) :6935-6939.
[12]Ling EM, Smith T, Nguyen XD, Pridgeon C, Dallman M, Arbery J, et al. Relation of CD4+CD25+regulatory T-cell suppression of allergendriven T-cell activation to atopic status and expression of allergic disease[J]. Lancet, 2004, 363(9409):608-615.
[14]Lin W, Truong N, Grossman WJ, Haribhai D, Williams CB, Wang J. Allergic dysregulation and hyperimmunoglobulin-emia E in Foxp3 mutant mice[J]. J Allergy Clin Immunol, 2005, 116(5):1106-1115.
[15]Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells[J]. Nat Immunol, 2003, 4(4):330-336.