Role of CD4+CD25+ Treg cells in chronic lung infection by Pseudomonas aeruginosa_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

YANG Qingmei , ZHANG Ping ,  SHEN Ce

Department of Respiratory Medicine，Shanghai Sixth People，s Hospital，Shanghai Jiao Tong University.Shanghai，200233，China Corresponding author：SHEN Ce，E-mail：yqingmay@yahoo.com.cn;

Corresponding author：

SHEN Ce, Email: yqingmay@yahoo.com.cn

Keywords：

Pseudomonas aeruginosa; CD4+CD25+ Treg cell; Chronic lung infection

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Objective To explore the role of CD4+CD25+ Treg cells in chronic pulmonary infection caused by Pseudomonas aeruginosa(PA).Methods Sixty SD rats were randomly divided into a PA group and a control group(n=30 in each group).Chronic lung infection model was established by implantation of silicone tube precoated with PA into the main bronchus.Twenty-eight days later Treg cells in peripheral blood were measured by fluorescence-activated cell sorting（FACS）.Levels of IL-10 and TGF-β in serum were assayed by ELISA.The expression of Foxp3 mRNA in spleen was measured by RT-PCR.Pathological changes of lung tissue were studed by HE staining.Results Treg/CD4+ T cells in the PA group were significantly more than those in the control group[（19.79±6.45）% vs （5.15±0.47）%，P lt;0.05].The levels of IL-10 and TGF-β were (231.52±54.48)pg/mL and （121.05±7.98）pg/mL in the PA group respectively，which were significantly higher than those in the control group[（35.43±23.56）pg/mL and （36.02±8.94）pg/mL].The expression of Foxp3 mRNA in the PA group was significantly higher compared with the control group(0.80±0.044 vs 0.25±0.054，P lt;0.05）.HE staining revealed that PA caused a intensive inflammatory reaction with lymphocytes infiltration.Conclusion CD4+CD25+ Treg cell is up-regulated and plays an important role in chronic lung infection caused by Pseudomonas aeruginosa.

Citation： YANG Qingmei,ZHANG Ping,SHEN Ce. Role of CD4+CD25+ Treg cells in chronic lung infection by Pseudomonas aeruginosa. Chinese Journal of Respiratory and Critical Care Medicine, 2008, 08(4): 286-289. doi: Copy

1.	MacDonald AJ，Duffy M，Brady MT，et al.CD4 T helper type 1 and regulatory T cells induced against the same epitopes on the core protein in hepatitis C virus-infected persons.J Infect Dis，2002，185：720-727.
2.	Sakaguchi S，Sakaguchi N，Asano M，et al.Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25).Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases.J Immunol.1995，155：1151-1164.
3.	Wickelgren I.Immunology.Policing the immune system.Science，2004，306：596-599.
4.	Kelsen J，Hvas CL，Agnholt J，et a1.CD4+ CD25+ regulatory T cells and their importance to human illnesses.Ugeskr Laeger2006，168：32-37.
5.	Moberg M，Gustavsson I，Gyllensten U.Type-specific associations of human papillomavirus load with risk of developing cervical carcinoma in situ.Int J Cancer，2004，112：854-859.
6.	杨青梅，张苹，沈策.铜绿假单胞菌慢性肺部感染模型的建立及评价.中国呼吸与危重监护杂志，2008，7：40-56.
7.	Belkaid Y，Rouse BT.Natural regulatory T cells in infectious disease.Nat Immunol.2005，6：353-360.
8.	Hisaeda H，Maekawa Y，Iwakawa D，et al.Escape of malaria parasites from host immunity requires CD4+ CD25+ regulatory T cells.Nat Med，2004，10：29-30.
9.	Dittmer U，He H，Messer RJ，et al.Functional impairment of CD8(+) T cells by regulatory T cells during persistent retroviral infection.Immunity，2004，20：293-303.
10.	Bantel H，Lügering A，Heidemann J，et al.Detection of apoptotic caspase activation in sera from patients with chronic HCV infection is associated with fibrotic liver injury.Hepatology.2004，40：1078-1087.
11.	Raghavan S，Fredriksson M，Svennerholm AM，et al.Absence of CD4+CD25+ regulatory T cells is associated with a loss of regulation leading to increased pathology in Helicobacter pylori-infected mice.Clin Exp Immunol.2003，132：393-400.
12.	Lundgren A，Suri-Payer E，Enarsson K，et al.Helicobacter pylori-specific CD4+ CD25high regulatory T cells suppress memory T-cell responses to H.pylori in infected individuals.Infect Immun，2003，71：1755-1762.
13.	Wisnoski N，Chung CS，Chen Y，et al.The contribution of CD4+ CD25+ T-regulatory-cells to immune suppression in sepsis.Shock，2007，27：251-257.
14.	Fontenot JD，Rudensky AY. A well adapted regulatory contrivance：regulatory T cell development and the forkhead family transcription factor Foxp3.Nat Immunol.2005，6：331-337.
15.	Cabrera R，Tu Z，Xu Y，et al.An immunomodulatory role for CD4(+)CD25(+) regulatory T lymphocytes in hepatitis C virus infection.Hepatology，2004，40：1062-1071.
16.	Joshi A，Vahlenkamp TW，Garg H，et al.Preferential replication of FIV in activated CD4(+)CD25(+)T cells independent of cellular proliferation.Virology，2004，321：307-322.
17.	Caramalho I，Lopes-Carvalho T，Ostler D，et al.Regulatory T cells selectively express toll-like receptors and are activated by lipopolysaccharide.J Exp Med，2003，197：403-411.

1. MacDonald AJ，Duffy M，Brady MT，et al.CD4 T helper type 1 and regulatory T cells induced against the same epitopes on the core protein in hepatitis C virus-infected persons.J Infect Dis，2002，185：720-727.
2. Sakaguchi S，Sakaguchi N，Asano M，et al.Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25).Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases.J Immunol.1995，155：1151-1164.
3. Wickelgren I.Immunology.Policing the immune system.Science，2004，306：596-599.
4. Kelsen J，Hvas CL，Agnholt J，et a1.CD4+ CD25+ regulatory T cells and their importance to human illnesses.Ugeskr Laeger2006，168：32-37.
5. Moberg M，Gustavsson I，Gyllensten U.Type-specific associations of human papillomavirus load with risk of developing cervical carcinoma in situ.Int J Cancer，2004，112：854-859.
6. 杨青梅，张苹，沈策.铜绿假单胞菌慢性肺部感染模型的建立及评价.中国呼吸与危重监护杂志，2008，7：40-56.
7. Belkaid Y，Rouse BT.Natural regulatory T cells in infectious disease.Nat Immunol.2005，6：353-360.
8. Hisaeda H，Maekawa Y，Iwakawa D，et al.Escape of malaria parasites from host immunity requires CD4+ CD25+ regulatory T cells.Nat Med，2004，10：29-30.
9. Dittmer U，He H，Messer RJ，et al.Functional impairment of CD8(+) T cells by regulatory T cells during persistent retroviral infection.Immunity，2004，20：293-303.
10. Bantel H，Lügering A，Heidemann J，et al.Detection of apoptotic caspase activation in sera from patients with chronic HCV infection is associated with fibrotic liver injury.Hepatology.2004，40：1078-1087.
11. Raghavan S，Fredriksson M，Svennerholm AM，et al.Absence of CD4+CD25+ regulatory T cells is associated with a loss of regulation leading to increased pathology in Helicobacter pylori-infected mice.Clin Exp Immunol.2003，132：393-400.
12. Lundgren A，Suri-Payer E，Enarsson K，et al.Helicobacter pylori-specific CD4+ CD25high regulatory T cells suppress memory T-cell responses to H.pylori in infected individuals.Infect Immun，2003，71：1755-1762.
13. Wisnoski N，Chung CS，Chen Y，et al.The contribution of CD4+ CD25+ T-regulatory-cells to immune suppression in sepsis.Shock，2007，27：251-257.
14. Fontenot JD，Rudensky AY. A well adapted regulatory contrivance：regulatory T cell development and the forkhead family transcription factor Foxp3.Nat Immunol.2005，6：331-337.
15. Cabrera R，Tu Z，Xu Y，et al.An immunomodulatory role for CD4(+)CD25(+) regulatory T lymphocytes in hepatitis C virus infection.Hepatology，2004，40：1062-1071.
16. Joshi A，Vahlenkamp TW，Garg H，et al.Preferential replication of FIV in activated CD4(+)CD25(+)T cells independent of cellular proliferation.Virology，2004，321：307-322.
17. Caramalho I，Lopes-Carvalho T，Ostler D，et al.Regulatory T cells selectively express toll-like receptors and are activated by lipopolysaccharide.J Exp Med，2003，197：403-411.

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Role of CD4+CD25+ Treg cells in chronic lung infection by Pseudomonas aeruginosa

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