A subset of circulating blood mycobacteria-specific CD4 T cells can predict the time to Mycobacterium tuberculosis sputum culture conversion.
A subset of circulating blood mycobacteria-specific CD4 T cells can predict the time to Mycobacterium tuberculosis sputum culture conversion.
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DOI：
10.1371/journal.pone.0102178
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Fallows D
中科院分区：
文献类型：
--
作者：
Riou C;Gray CM;Lugongolo M;Gwala T;Kiravu A;Deniso P;Stewart-Isherwood L;Omar SV;Grobusch MP;Coetzee G;Conradie F;Ismail N;Kaplan G;Fallows D
我们调查了18名hiv阴性的耐多药结核病患者的结核分枝杆菌（Mtb）和ppd特异性CD4 T细胞反应，并对他们进行了为期6个月的药物治疗。其中12例患者痰培养（SC）阳性，6例患者入组时SC阴性。我们的目的是鉴定分枝杆菌特异性CD4 T细胞的一个亚群，该亚群可以预测培养转化的时间。基线时分枝杆菌特异性CD4 T细胞的总频率不能区分SC阳性或阴性患者，但SC阳性患者中Mtb和ppd特异性记忆CD4 T细胞的比例高于SC阴性患者（p = 0.004和p = 0.0012）。同样，HLA-DR+Ki67+在Mtb和ppd特异性CD4 T细胞上的高共表达也可以区分痰SC阳性和SC阴性（分别为p = 0.004和p = 0.001）。受试者工作特征（ROC）分析显示，Ki67+HLA-DR+ Mtb和ppd特异性CD4 T细胞的基线水平可预测痰培养转化时间，曲线下面积为0.8 （p = 0.027）。在治疗后的前2个月，Ki67+HLA-DR+ T细胞群显著下降，6个月后，分枝杆菌特异性多功能IFNγ+IL2+TNFα+ CD4 T细胞逐渐增加。因此，激活和增殖的分枝杆菌特异性CD4 T细胞亚群（Ki67+HLA-DR+）可能在外周血中提供有价值的标记物，预测结核病患者在治疗开始时的痰培养转化时间。
We investigated 18 HIV-negative patients with MDR-TB for M. tuberculosis (Mtb)- and PPD-specific CD4 T cell responses and followed them over 6 months of drug therapy. Twelve of these patients were sputum culture (SC) positive and six patients were SC negative upon enrollment. Our aim was to identify a subset of mycobacteria-specific CD4 T cells that would predict time to culture conversion. The total frequency of mycobacteria-specific CD4 T cells at baseline could not distinguish patients showing positive or negative SC. However, a greater proportion of late-differentiated (LD) Mtb- and PPD-specific memory CD4 T cells was found in SC positive patients than in those who were SC negative (p = 0.004 and p = 0.0012, respectively). Similarly, a higher co-expression of HLA-DR+Ki67+ on Mtb- and PPD-specific CD4 T cells could also discriminate between sputum SC positive versus SC negative (p = 0.004 and p = 0.001, respectively). Receiver operating characteristic (ROC) analysis revealed that baseline levels of Ki67+HLA-DR+ Mtb- and PPD-specific CD4 T cells were predictive of the time to sputum culture conversion, with area-under-the-curve of 0.8 (p = 0.027). Upon treatment, there was a significant decline of these Ki67+HLA-DR+ T cell populations in the first 2 months, with a progressive increase in mycobacteria-specific polyfunctional IFNγ+IL2+TNFα+ CD4 T cells over 6 months. Thus, a subset of activated and proliferating mycobacterial-specific CD4 T cells (Ki67+HLA-DR+) may provide a valuable marker in peripheral blood that predicts time to sputum culture conversion in TB patients at the start of treatment.
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影响因子：
82.9
作者：
Harari A;Rozot V;Bellutti Enders F;Perreau M;Stalder JM;Nicod LP;Cavassini M;Calandra T;Blanchet CL;Jaton K;Faouzi M;Day CL;Hanekom WA;Bart PA;Pantaleo G
通讯作者：
Pantaleo G
DOI：
10.4049/jimmunol.1101122
发表时间：
2011-09-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Day CL;Abrahams DA;Lerumo L;Janse van Rensburg E;Stone L;O'rie T;Pienaar B;de Kock M;Kaplan G;Mahomed H;Dheda K;Hanekom WA
通讯作者：
Hanekom WA
影响因子：
3.2
作者：
Ottenhoff, Tom H. M.;Ellner, Jerrold J.;Kaufmann, Stefan H. E.
通讯作者：
Kaufmann, Stefan H. E.
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
9.1
作者：
Jiang, Jing;Wang, Xianyuan;Cheng, Xiaoxing
通讯作者：
Cheng, Xiaoxing