CD4+CD25+調節性T細胞在銅綠假單胞菌慢性肺部感染中的變化及其意義_《中國呼吸與危重監護雜志》

作者：

楊青梅 , 張蘋 ,  沈策

上海交通大學附屬第六人民醫院肺內科（上海 200233）;

關鍵詞：

CD4+CD25+調節性T細胞銅綠假單胞菌慢性肺部感染

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目的探討CD4+CD25+調節性T細胞（CD4+CD25+ Treg細胞）在銅綠假單胞菌（PA）慢性肺部感染中的變化及意義。方法 60只雄性SD大鼠隨機分為PA感染組和空白對照組。將PA包被的硅膠管置入大鼠一側主支氣管建立慢性肺部感染模型，對照組置入無菌硅膠管。28 d后，熒光激活細胞分類（FACS）檢測外周血CD4+CD25+ Treg細胞數量，ELISA檢測血清白細胞介素-10（IL-10）和轉化生長因子-β（TGF-β）水平，RT-PCR檢測脾臟Foxp3 mRNA表達，肺組織行HE染色觀察組織病理學變化。結果 PA感染組Treg/CD4+T淋巴細胞的百分比明顯高于對照組[（19.79±6.45）%比（5.15±0.47）%，P lt;0.05]。PA感染組血清IL-10和TGF-β水平均顯著高于對照組[IL-10：（231.52±54.48）pg/mL比（35.43±23.56）pg/mL，P lt;0.05；TGF-β：（121.05±7.98）pg/mL比（36.02±8.94）pg/mL，P lt;0.05]。PA感染組Foxp3 mRNA相對含量較對照組顯著升高[（0.80±0.044）比（0.25±0.054），P lt;0.05]。HE染色見PA感染組肺組織有大量淋巴細胞聚集，纖維增生明顯，膿腫形成。結論 CD4+CD25+ Treg細胞在PA慢性肺部感染時數量增多、功能增強，對感染慢性化形成有重要影響。

引用本文： 楊青梅,張蘋,沈策. CD4+CD25+調節性T細胞在銅綠假單胞菌慢性肺部感染中的變化及其意義. 中國呼吸與危重監護雜志, 2008, 08(4): 286-289. doi: 復制

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.	楊青梅，張蘋，沈策.銅綠假單胞菌慢性肺部感染模型的建立及評價.中國呼吸與危重監護雜志，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. 楊青梅，張蘋，沈策.銅綠假單胞菌慢性肺部感染模型的建立及評價.中國呼吸與危重監護雜志，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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CD4+CD25+調節性T細胞在銅綠假單胞菌慢性肺部感染中的變化及其意義

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《中國呼吸與危重監護雜志》

CD4+CD25+調節性T細胞在銅綠假單胞菌慢性肺部感染中的變化及其意義

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