Identification of the predominant human NK cell effector subset mediating ADCC against HIV-infected targets coated with BNAbs or plasma from PLWH.
Identification of the predominant human NK cell effector subset mediating ADCC against HIV-infected targets coated with BNAbs or plasma from PLWH.
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DOI：
10.1002/eji.202149188
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发表时间：
2021-08
影响因子：
5.4
通讯作者：
Montaner LJ
中科院分区：
文献类型：
--
作者：
Tomescu C;Kroll K;Colon K;Papasavvas E;Frank I;Tebas P;Mounzer K;Reeves RK;Montaner LJ
利用BNAb如3BNC 117和10-1074限制病毒复制同时还促进HIV感染细胞的清除的免疫治疗策略的潜力提高了对鉴定能够介导抗体依赖性细胞毒性（ADCC）的主要NK效应子亚群的兴趣。利用高级多色流式细胞术，我们确定ART抑制PLWH的CD 57阳性NK细胞表达显著更高水平的CD 16 FcγR受体、2B 4 ADCC共受体和HLA-DR活化标志物，而NKG 2C阳性NK细胞表达显著更高水平的CD 2 ADCC共受体（p<0.001，n=32）。在功能上，与CD 57阴性NK细胞相比，来自ART抑制PLWH且具有高或低NKG 2C扩增的CD 57阳性NK细胞表现出显著增强的脱粒和IFN-γ产生，其针对HIV参比血浆包被的异源gp 120包被ADCC靶标（p=0.002，n=11）。来自缺乏NKG 2C扩增的对照供体的CD 57阳性NK细胞在针对异源ADCC靶标（p=0.019，n=9）和用BNAb包被的HIV-1感染的自体CD 4+原代T细胞检测的每个时间点也显示出显著更多的脱粒和IFN-γ产生。总之，我们的数据支持CD 57阳性和NKG 2C阳性NK细胞作为主要的ADCC效应子亚群，能够在3BNC 117和10-1074免疫治疗的存在下靶向HIV感染的CD 4+细胞。我们研究了可以利用BNAb通过ADCC清除HIV感染靶点的NK效应子亚群。在对照供体中，我们鉴定了CD 57 pos成熟NK细胞对包被有BNAb的HIV-1感染的靶标表现出最大的ADCC多功能性，而NKG 2Cpos/CD 57 pos适应性NK细胞在PLWH中也表现出较强的ADCC能力。
The potential of immunotherapy strategies utilizing BNAbs such as 3BNC117 and 10–1074 to limit viral replication while also facilitating clearance of HIV infected cells has heightened interest in identifying the predominant NK effector subset(s) capable of mediating Antibody Dependent Cellular Cytotoxicity (ADCC). Utilizing Advanced Poly-chromatic Flow Cytometry, we identified that CD57 positive NK cells from ART-suppressed PLWH expressed significantly higher levels of the CD16 FcγR Receptor, 2B4 ADCC co-receptor and HLA-DR activation marker while NKG2C positive NK cells expressed significantly higher levels of the CD2 ADCC co-receptor (p<0.001, n=32). Functionally, CD57 positive NK cells from ART-suppressed PLWH with either high or low NKG2C expansion exhibited significantly enhanced degranulation and IFN-gamma production against heterologous gp120-coated ADCC targets coated with HIV reference plasma compared to CD57 negative NK cells (p=0.002, n=11). CD57 positive NK cells from control donors lacking NKG2C expansion also exhibited significantly more degranulation and IFN-gamma production at every timepoint tested against both heterologous ADCC targets (p=0.019, n=9) and HIV-1 infected autologous CD4+ primary T cells coated with BNAbs. Together, our data supports CD57 positive and NKG2C positive NK cells as the predominant ADCC effector subsets capable of targeting HIV-infected CD4+ cells in the presence of 3BNC117 and 10–1074 immunotherapy. We investigated the NK effector subset(s) that can utilize BNAbs in clearance of HIV-infected targets through ADCC. In control donors, we identified CD57pos mature NK cells exhibited the greatest ADCC poly-functionality against HIV-1 infected targets coated with BNAbs, while NKG2Cpos/CD57pos adaptive NK cells also exhibited strong ADCC capacity in PLWH.
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DOI：
10.4049/jimmunol.1303211
发表时间：
2014-05-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Hendricks DW;Balfour HH Jr;Dunmire SK;Schmeling DO;Hogquist KA;Lanier LL
通讯作者：
Lanier LL
影响因子：
16.6
作者：
Bruel T;Guivel-Benhassine F;Amraoui S;Malbec M;Richard L;Bourdic K;Donahue DA;Lorin V;Casartelli N;Noël N;Lambotte O;Mouquet H;Schwartz O
通讯作者：
Schwartz O
影响因子：
4.7
作者：
Comeau, Emilie M.;Holder, Kayla A.;Grant, Michael D.
通讯作者：
Grant, Michael D.
影响因子：
64.8
作者：
Caskey M;Klein F;Lorenzi JC;Seaman MS;West AP Jr;Buckley N;Kremer G;Nogueira L;Braunschweig M;Scheid JF;Horwitz JA;Shimeliovich I;Ben-Avraham S;Witmer-Pack M;Platten M;Lehmann C;Burke LA;Hawthorne T;Gorelick RJ;Walker BD;Keler T;Gulick RM;Fätkenheuer G;Schlesinger SJ;Nussenzweig MC
通讯作者：
Nussenzweig MC
影响因子：
3.8
作者：
Bonaparte, MI;Barker, E
通讯作者：
Barker, E