Infectious Complications Predict Premature CD8(+) T-cell Senescence in CD40 Ligand-Deficient Patients.
Infectious Complications Predict Premature CD8(+) T-cell Senescence in CD40 Ligand-Deficient Patients.
复制标题
DOI：
10.1007/s10875-021-00968-x
复制
发表时间：
2021-05
影响因子：
9.1
通讯作者：
Kang I
中科院分区：
文献类型：
--
作者：
Shin JJ;Catanzaro J;Yonkof JR;Delmonte O;Sacco K;Shin MS;Reddy S;Whittington PJ;Soffer G;Mustillo PJ;Sullivan KE;Notarangelo LD;Abraham RS;Romberg N;Kang I
CD 40配体（CD 40 L）缺乏的患者表现出对感染的易感性增加，可以通过有效的预防策略（包括免疫球蛋白G（IgG）替代和预防性抗生素）来缓解。CD 8 + T细胞衰老在CD 40 L缺乏症中有描述，但尚不清楚这是疾病的内在特征还是继发于感染暴露。为了解决这个问题，我们评估了CD 40 L缺陷患者的CD 8 + T细胞衰老及其与临床病史的关系，包括预防依从性和感染。使用T细胞受体切除环（TREC）分析、流式细胞术、飞行时间流式细胞术（CyTOF）和体外功能测定（包括CMV特异性增殖和细胞因子释放测定）评估来自7名CD 40 L缺陷患者和健康对照（HC）的外周CD 8 + T细胞的衰老特征。3例免疫球蛋白G替代和耶氏肺孢子虫肺炎（PJP）预防粘附性差和/或发生多发性儿童肺炎（患者组1）的患者（5、28和34岁）与HC相比，具有衰老表型的效应记忆CD 8 + T细胞扩增。在患者组2（4例患者，16岁、22岁、24岁和33岁）中未观察到此类变化，这些患者终身坚持预防治疗，感染并发症很少。来自5岁患者和老年人HC的CD 8 + T细胞的CyTOF分析显示衰老相关分子的表达模式相似。我们的研究结果支持，复发性感染和不遵守预防促进早期CD 8 + T细胞衰老的CD 40 L缺乏症。过早衰老可能会增加恶性易感性，并进一步加剧CD 40 L缺陷患者的感染风险。
CD40 ligand (CD40L)-deficient patients display increased susceptibilities to infections that can be mitigated with effective prophylactic strategies including immunoglobulin G (IgG) replacement and prophylactic antibiotics. CD8+ T-cell senescence has been described in CD40L deficiency, but it is unclear if this is an intrinsic feature of the disease or secondary to infectious exposures. To address this question, we assessed CD8+ T-cell senescence and its relationship to clinical histories, including prophylaxis adherence and infections, in CD40L-deficient patients. Peripheral CD8+ T-cells from seven CD40L-deficient patients and healthy controls (HCs) were assessed for senescent features using T-cell receptor excision circle (TREC) analysis, flow cytometry, cytometry by time of flight (CyTOF) and in vitro functional determinations including CMV-specific proliferation and cytokine release assays. Three patients (5, 28, and 34 years old) who were poorly adherent to immunoglobulin G replacement and Pneumocystis jirovecii pneumonia (PJP) prophylaxis and/or experienced multiple childhood pneumonias (patient group 1) had an expansion of effector memory CD8+ T-cells with the senescent phenotype when compared to HCs. Such changes were not observed in the patient group 2 (four patients, 16, 22, 24, and 33 years old) who were life-long adherents to prophylaxis and experienced few infectious complications. CyTOF analysis of CD8+ T-cells from the 5-year-old patient and older adult HCs showed similar expression patterns of senescence-associated molecules. Our findings support that recurrent infections and non-adherence to prophylaxis promote early CD8+ T-cell senescence in CD40L deficiency. Premature senescence may increase malignant susceptibilities and further exacerbate infectious risk in CD40L-deficient patients.
登录
查看更多内容
影响因子：
3.7
作者：
Paquin-Proulx D;Santos BA;Carvalho KI;Toledo-Barros M;Barreto de Oliveira AK;Kokron CM;Kalil J;Moll M;Kallas EG;Sandberg JK
通讯作者：
Sandberg JK
DOI：
10.1016/j.jaci.2016.06.021
发表时间：
2017-02
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Coulter TI;Chandra A;Bacon CM;Babar J;Curtis J;Screaton N;Goodlad JR;Farmer G;Steele CL;Leahy TR;Doffinger R;Baxendale H;Bernatoniene J;Edgar JD;Longhurst HJ;Ehl S;Speckmann C;Grimbacher B;Sediva A;Milota T;Faust SN;Williams AP;Hayman G;Kucuk ZY;Hague R;French P;Brooker R;Forsyth P;Herriot R;Cancrini C;Palma P;Ariganello P;Conlon N;Feighery C;Gavin PJ;Jones A;Imai K;Ibrahim MA;Markelj G;Abinun M;Rieux-Laucat F;Latour S;Pellier I;Fischer A;Touzot F;Casanova JL;Durandy A;Burns SO;Savic S;Kumararatne DS;Moshous D;Kracker S;Vanhaesebroeck B;Okkenhaug K;Picard C;Nejentsev S;Condliffe AM;Cant AJ
通讯作者：
Cant AJ
淋巴结host的效应CD8+ T细胞植入和抗肿瘤免疫是IL7Rα的依赖性。
影响因子：
10.1
作者：
Johnson CB;Riesenberg BP;May BR;Gilreath SC;Li G;Staveley-O'Carroll KF;Garrett-Mayer E;Mehrotra S;Cole DJ;Rubinstein MP
通讯作者：
Rubinstein MP
影响因子：
5.5
作者：
Kim, Jung-Sik;Cho, Bon-A;Kim, Hang-Rae
通讯作者：
Kim, Hang-Rae
CD40-CD40配体相互作用在粘膜CD8 T细胞反应扩增中的关键作用。
影响因子：
15.3
作者：
Lefrancois, L;Olson, S;Masopust, D
通讯作者：
Masopust, D