Polymicrobial Sepsis Chronic Immunoparalysis Is Defined by Diminished Ag-Specific T Cell-Dependent B Cell Responses.
Polymicrobial Sepsis Chronic Immunoparalysis Is Defined by Diminished Ag-Specific T Cell-Dependent B Cell Responses.
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DOI：
10.3389/fimmu.2018.02532
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发表时间：
2018
影响因子：
7.3
通讯作者：
Griffith TS
中科院分区：
文献类型：
--
作者：
Sjaastad FV;Condotta SA;Kotov JA;Pape KA;Dail C;Danahy DB;Kucaba TA;Tygrett LT;Murphy KA;Cabrera-Perez J;Waldschmidt TJ;Badovinac VP;Griffith TS
免疫抑制是脓毒症的一个标志，降低宿主对原发性脓毒症病原体和/或继发性医院感染的反应。CD 4 T细胞和B细胞是在脓毒症期间经历数量和功能减少的免疫细胞阵列中的一种。从滤泡辅助（Tfh）CD 4 T细胞到B细胞的“帮助”是生产性和保护性体液免疫所必需的，但是定义脓毒症对主要CD 4 T细胞依赖性B细胞应答的影响的数据很少。使用盲肠结扎和穿孔（CLP）脓毒症诱导小鼠模型，我们观察到与接受假手术的小鼠相比，CLP手术后早期（2天）和晚期（30天）用A型流感病毒或TNP-KLH明矾激发的小鼠抗体产生减少。为了更好地理解这些CD 4 T细胞依赖性B细胞应答如何被脓毒症事件改变，我们用含有MHC II限制性肽2 W1 S56 −68与荧光染料藻红蛋白（PE）偶联的完全弗氏佐剂乳剂免疫小鼠。用2 W1 S-PE/CFA免疫导致T细胞依赖性B细胞活化，使我们能够在同一小鼠中追踪对相同免疫原应答的抗原特异性CD 4 T细胞和B细胞的限定群体。与假手术小鼠相比，CLP手术小鼠PE特异性B细胞的分化和类别转换减弱。类似地，CLP小鼠在免疫后2 W1 S特异性T细胞的扩增和Tfh分化减少。我们的数据表明，CLP诱导的脓毒症通过影响抗原特异性B细胞和CD 4 Tfh细胞的数量和功能来影响体液免疫，进一步确定脓毒症诱导后的慢性免疫麻痹期。
Immunosuppression is one hallmark of sepsis, decreasing the host response to the primary septic pathogens and/or secondary nosocomial infections. CD4 T cells and B cells are among the array of immune cells that experience reductions in number and function during sepsis. “Help” from follicular helper (Tfh) CD4 T cells to B cells is needed for productive and protective humoral immunity, but there is a paucity of data defining the effect of sepsis on a primary CD4 T cell-dependent B cell response. Using the cecal ligation and puncture (CLP) mouse model of sepsis induction, we observed reduced antibody production in mice challenged with influenza A virus or TNP-KLH in alum early (2 days) and late (30 days) after CLP surgery compared to mice subjected to sham surgery. To better understand how these CD4 T cell-dependent B cell responses were altered by a septic event, we immunized mice with a Complete Freund's Adjuvant emulsion containing the MHC II-restricted peptide 2W1S56−68 coupled to the fluorochrome phycoerythrin (PE). Immunization with 2W1S-PE/CFA results in T cell-dependent B cell activation, giving us the ability to track defined populations of antigen-specific CD4 T cells and B cells responding to the same immunogen in the same mouse. Compared to sham mice, differentiation and class switching in PE-specific B cells were blunted in mice subjected to CLP surgery. Similarly, mice subjected to CLP had reduced expansion of 2W1S-specific T cells and Tfh differentiation after immunization. Our data suggest CLP-induced sepsis impacts humoral immunity by affecting the number and function of both antigen-specific B cells and CD4 Tfh cells, further defining the period of chronic immunoparalysis after sepsis induction.
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DOI：
10.4049/jimmunol.1101180
发表时间：
2011-09-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Gurung P;Rai D;Condotta SA;Babcock JC;Badovinac VP;Griffith TS
通讯作者：
Griffith TS
影响因子：
120.7
作者：
Boomer, Jonathan S.;To, Kathleen;Chang, Kathy C.;Takasu, Osamu;Osborne, Dale F.;Walton, Andrew H.;Bricker, Traci L.;Jarman, Stephen D., II;Kreisel, Daniel;Krupnick, Alexander S.;Srivastava, Anil;Swanson, Paul E.;Green, Jonathan M.;Hotchkiss, Richard S.
通讯作者：
Hotchkiss, Richard S.
DOI：
10.1038/nri3552
发表时间：
2013-12
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
8.6
作者：
De, AK;Kodys, KM;Miller-Graziano, CL
通讯作者：
Miller-Graziano, CL
影响因子：
5.5
作者：
HogenEsch, H
通讯作者：
HogenEsch, H