Production of Proinflammatory Cytokines by CD4+ and CD8+ T Cells in Response to Mycobacterial Antigens among Children and Adults with Tuberculosis.
Production of Proinflammatory Cytokines by CD4+ and CD8+ T Cells in Response to Mycobacterial Antigens among Children and Adults with Tuberculosis.
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DOI：
10.3390/pathogens12111353
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发表时间：
2023-11-14
期刊：
影响因子：
--
通讯作者：
Lancioni CL
中科院分区：
文献类型：
--
作者：
Morrow E;Liu Q;Kiguli S;Swarbrick G;Nsereko M;Null MD;Cansler M;Mayanja-Kizza H;Boom WH;Chheng P;Nyendak MR;Lewinsohn DM;Lewinsohn DA;Lancioni CL
由结核分枝杆菌（Mtb）引起的结核病（TB）仍然是儿科发病率和死亡率的主要原因。幼儿暴露于结核分枝杆菌后患结核病的风险很高，这种脆弱性是继发于生命早期宿主免疫力不足。我们的主要目的是比较乌干达确诊结核病成人（n = 41）和乌干达确诊结核病（n = 12）和未确诊结核病（n = 41）的年轻儿童对6种分枝杆菌抗原和超抗原葡萄球菌肠毒素B（SE B）应答时促炎细胞因子IFN-γ、IL-2和TNF-α的CD 4+和CD 8 + T细胞产生，非结核性下呼吸道感染39例。流式细胞术用于鉴定和定量响应于每种分枝杆菌抗原和SEB的CD 4+和CD 8 + T细胞细胞因子的产生。我们发现，与成人相比，所有儿科队列中响应于SEB的CD 4+和CD 8 + T细胞产生细胞因子的频率均降低。然而，T细胞对Mtb特异性抗原ESAT 6和CFP 10的反应在儿童和确诊TB的成人之间是等同的。与此相反，ESAT 6和CFP 10的细胞因子产生在未确诊的TB儿童中是有限的，而在非TB下呼吸道感染的儿童中是不存在的。在测试的五种额外的分枝杆菌抗原中，PE 3和PPE 15被广泛识别，而不管TB疾病分类和年龄。在开始TB治疗之前，确诊TB的儿童对Mtb特异性抗原表现出强烈的促炎性CD 4+和CD 8 + T细胞应答。我们的研究结果表明，适应性促炎性免疫反应Mtb，其特征在于T细胞产生IFN-γ，IL-2和TNF-α，在生命早期不受损害。
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a leading cause of pediatric morbidity and mortality. Young children are at high risk of TB following Mtb exposure, and this vulnerability is secondary to insufficient host immunity during early life. Our primary objective was to compare CD4+ and CD8+ T-cell production of proinflammatory cytokines IFN-gamma, IL-2, and TNF-alpha in response to six mycobacterial antigens and superantigen staphylococcal enterotoxin B (SEB) between Ugandan adults with confirmed TB (n = 41) and young Ugandan children with confirmed (n = 12) and unconfirmed TB (n = 41), as well as non-TB lower respiratory tract infection (n = 39). Flow cytometry was utilized to identify and quantify CD4+ and CD8+ T-cell cytokine production in response to each mycobacterial antigen and SEB. We found that the frequency of CD4+ and CD8+ T-cell production of cytokines in response to SEB was reduced in all pediatric cohorts when compared to adults. However, T-cell responses to Mtb-specific antigens ESAT6 and CFP10 were equivalent between children and adults with confirmed TB. In contrast, cytokine production in response to ESAT6 and CFP10 was limited in children with unconfirmed TB and absent in children with non-TB lower respiratory tract infection. Of the five additional mycobacterial antigens tested, PE3 and PPE15 were broadly recognized regardless of TB disease classification and age. Children with confirmed TB exhibited robust proinflammatory CD4+ and CD8+ T-cell responses to Mtb-specific antigens prior to the initiation of TB treatment. Our findings suggest that adaptive proinflammatory immune responses to Mtb, characterized by T-cell production of IFN-gamma, IL-2, and TNF-alpha, are not impaired during early life.
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DOI：
10.1093/infdis/jix362
发表时间：
2017-11-03
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Churchyard G;Kim P;Shah NS;Rustomjee R;Gandhi N;Mathema B;Dowdy D;Kasmar A;Cardenas V
通讯作者：
Cardenas V
影响因子：
38.2
作者：
Huang, Zhen;LaCourse, Sylvia M.;Kay, Alexander W.;Stern, Joshua;Escudero, Jaclyn N.;Youngquist, Brady M.;Zheng, Wenshu;Vambe, Debrah;Dlamini, Muyalo;Mtetwa, Godwin;Cranmer, Lisa M.;Njuguna, Irene;Wamalwa, Dalton C.;Maleche-Obimbo, Elizabeth;Catanzaro, Donald G.;Lyon, Christopher J.;John-Stewart, Grace;DiNardo, Andrew;Mandalakas, Anna M.;Ning, Bo;Hu, Tony Y.
通讯作者：
Hu, Tony Y.
影响因子：
20.3
作者：
Godfrey, WR;Spoden, DJ;Porter, SB
通讯作者：
Porter, SB
DOI：
10.1164/rccm.201003-0334oc
发表时间：
2010-10-15
影响因子：
24.7
作者：
Kagina, Benjamin M. N.;Abel, Brian;Hanekom, Willem A.
通讯作者：
Hanekom, Willem A.
影响因子：
4.3
作者：
BRYSON, YJ;WINTER, HS;STIEHM, ER
通讯作者：
STIEHM, ER