Genetic Defects in Phosphoinositide 3-Kinase δ Influence CD8(+) T Cell Survival, Differentiation, and Function.
Genetic Defects in Phosphoinositide 3-Kinase δ Influence CD8(+) T Cell Survival, Differentiation, and Function.
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DOI：
10.3389/fimmu.2018.01758
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发表时间：
2018
影响因子：
7.3
通讯作者：
Schwartzberg PL
中科院分区：
文献类型：
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作者：
Cannons JL;Preite S;Kapnick SM;Uzel G;Schwartzberg PL
活化磷酸肌肽3-激酶δ综合征（Activated phosphoinositide 3-kinase delta syndrome， APDS），又称p110δ活化突变引起的衰老T细胞、淋巴结病和免疫缺陷（PASLI），是一种常染色体显性的原发性人类免疫缺陷（PID），由编码PI3K的p110δ催化亚基的PIK3CD杂合性功能获得突变引起。最近描述的这种PID的特点是多种多样的临床表现，包括复发性呼吸道感染、淋巴细胞增殖、进行性淋巴细胞减少和抗体反应缺陷。在NIH队列中观察到的PIK3CD突变患者的主要临床表现是慢性eb病毒和/或巨细胞病毒血症。尽管EBV感染不受控制，但许多APDS/PASLI患者的EBV特异性CD8+ T细胞频率正常或更高。在这篇综述中，我们讨论了与APDS/PASLI中CD8+ T细胞功能相关的数据，包括细胞死亡增加、衰竭标志物的表达和自体ebv感染B细胞的杀伤改变，以及这些数据和其他关于PI3K的数据如何为阻止慢性感染清除的潜在细胞缺陷提供见解。
Activated phosphoinositide 3-kinase delta syndrome (APDS), also known as p110 delta-activating mutation causing senescent T cells, lymphadenopathy and immunodeficiency (PASLI), is an autosomal dominant primary human immunodeficiency (PID) caused by heterozygous gain-of-function mutations in PIK3CD, which encodes the p110δ catalytic subunit of PI3K. This recently described PID is characterized by diverse and heterogeneous clinical manifestations that include recurrent respiratory infections, lymphoproliferation, progressive lymphopenia, and defective antibody responses. A major clinical manifestation observed in the NIH cohort of patients with PIK3CD mutations is chronic Epstein–Barr virus (EBV) and/or cytomegalovirus viremia. Despite uncontrolled EBV infection, many APDS/PASLI patients had normal or higher frequencies of EBV-specific CD8+ T cells. In this review, we discuss data pertaining to CD8+ T cell function in APDS/PASLI, including increased cell death, expression of exhaustion markers, and altered killing of autologous EBV-infected B cells, and how these and other data on PI3K provide insight into potential cellular defects that prevent clearance of chronic infections.
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影响因子：
64.5
作者：
Brunet, A;Bonni, A;Greenberg, ME
通讯作者：
Greenberg, ME
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
影响因子：
64.8
作者：
Im SJ;Hashimoto M;Gerner MY;Lee J;Kissick HT;Burger MC;Shan Q;Hale JS;Lee J;Nasti TH;Sharpe AH;Freeman GJ;Germain RN;Nakaya HI;Xue HH;Ahmed R
通讯作者：
Ahmed R
DOI：
10.1126/science.1243292
发表时间：
2013-11-15
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Angulo I;Vadas O;Garçon F;Banham-Hall E;Plagnol V;Leahy TR;Baxendale H;Coulter T;Curtis J;Wu C;Blake-Palmer K;Perisic O;Smyth D;Maes M;Fiddler C;Juss J;Cilliers D;Markelj G;Chandra A;Farmer G;Kielkowska A;Clark J;Kracker S;Debré M;Picard C;Pellier I;Jabado N;Morris JA;Barcenas-Morales G;Fischer A;Stephens L;Hawkins P;Barrett JC;Abinun M;Clatworthy M;Durandy A;Doffinger R;Chilvers ER;Cant AJ;Kumararatne D;Okkenhaug K;Williams RL;Condliffe A;Nejentsev S
通讯作者：
Nejentsev S
DOI：
10.1038/nri2888
发表时间：
2011-02
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
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