Regulation of virus-specific CD4+ T cell function by multiple costimulatory receptors during chronic HIV infection.
Regulation of virus-specific CD4+ T cell function by multiple costimulatory receptors during chronic HIV infection.
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在慢性HIV感染过程中，通过多种共刺激受体调节病毒特异性CD4+ T细胞功能。
DOI：
10.4049/jimmunol.1000156
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发表时间：
2010-09-01
期刊：
影响因子：
--
通讯作者：
Palmer BE
中科院分区：
文献类型：
--
作者：
Kassu A;Marcus RA;D'Souza MB;Kelly-McKnight EA;Golden-Mason L;Akkina R;Fontenot AP;Wilson CC;Palmer BE
病毒特异性T细胞上抑制性受体的表达升高被认为是病毒逃避宿主免疫监视的机制。在慢性感染期间阻断这些途径导致T细胞功能增加和病毒复制的免疫控制改善。为了探讨共刺激受体与HIV复制之间的关系，我们检测了HIV感染者的HIV特异性CD 4 + T细胞上程序性死亡1（PD-1）、CTLA-4、T细胞IG结构域和粘蛋白结构域3（TIM-3）以及CD 28的表达。来自未治疗受试者的超过30%的HIV特异性CD4 + T细胞共表达PD-1、CTLA-4和TIM-3，而<2%的CMV或水痘带状疱疹病毒特异性CD4 + T细胞表达所有三种受体。HIV特异性CD4 + T细胞上所有三种抑制性受体的共表达与病毒载量的相关性比每种受体单独表达的相关性更强。抗逆转录病毒治疗对HIV复制的抑制与HIV特异性CD4 + T细胞上所有三种抑制性受体表达的降低有关。令人惊讶的是，表达抑制性受体的HIV特异性CD4 + T细胞的高百分比也共表达CD28。在体外阻断PD-1结合的同时通过CD28刺激，协同增加HIV特异性CD4 + T细胞增殖的程度比单独使用更大。这些研究结果表明，HIV特异性的CD4 + T细胞反应在慢性感染的调节复杂的模式共表达的抑制性受体和抑制性受体的阻断和共刺激受体的刺激的协同作用，可用于治疗增强HIV特异性的CD4 + T细胞功能。
Elevated expression of inhibitory receptors on virus-specific T cells has been implicated as a mechanism by which viruses evade host immune surveillance. Blockade of these pathways during chronic infection leads to increased T cell function and improved immune control of viral replication. To explore the association between costimulatory receptors and HIV replication, we examined the expression of programmed death 1 (PD-1), CTLA-4, T cell Ig domain and mucin domain 3 (TIM-3), and CD28 on HIV-specific CD4+ T cells from HIV-infected subjects. Greater than 30% of HIV-specific CD4+ T cells from untreated subjects coexpressed PD-1, CTLA-4, and TIM-3, whereas <2% of CMV- or varicella-zoster virus-specific CD4+ T cells expressed all three receptors. Coexpression of all three inhibitory receptors on HIV-specific CD4+ T cells was more strongly correlated with viral load compared with the expression of each receptor individually. Suppression of HIV replication with antiretroviral therapy was associated with decreased expression of all three inhibitory receptors on HIV-specific CD4+ T cells. Surprisingly, a high percentage of HIV-specific CD4+ T cells that expressed inhibitory receptors also coexpressed CD28. In vitro blockade of PD-1 binding concurrent with stimulation through CD28 synergistically increased HIV-specific CD4+ T cell proliferation to a greater extent than did either alone. These findings indicate that HIV-specific CD4+ T cell responses during chronic infection are regulated by complex patterns of coexpressed inhibitory receptors and that the synergistic effect of inhibitory receptor blockade and stimulation of costimulatory receptors could be used for therapeutic augmentation of HIV-specific CD4+ T cell function.
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影响因子：
8.6
作者：
Kassu, Afework;D'Souza, Michelle;Palmer, Brent E.
通讯作者：
Palmer, Brent E.
影响因子：
30.5
作者：
Blackburn, Shawn D.;Shin, Haina;Haining, W. Nicholas;Zou, Tao;Workman, Creg J.;Polley, Antonio;Betts, Michael R.;Freeman, Gordon J.;Vignali, Dario A. A.;Wherry, E. John
通讯作者：
Wherry, E. John
影响因子：
20.3
作者：
Hryniewicz, Anna;Boasso, Adriano;Franchini, Genoveffa
通讯作者：
Franchini, Genoveffa
影响因子：
64.8
作者：
Day, Cheryl L.;Kaufmann, Daniel E.;Walker, Bruce D.
通讯作者：
Walker, Bruce D.
DOI：
10.1084/jem.20081398
发表时间：
2008-11-24
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Jones RB;Ndhlovu LC;Barbour JD;Sheth PM;Jha AR;Long BR;Wong JC;Satkunarajah M;Schweneker M;Chapman JM;Gyenes G;Vali B;Hyrcza MD;Yue FY;Kovacs C;Sassi A;Loutfy M;Halpenny R;Persad D;Spotts G;Hecht FM;Chun TW;McCune JM;Kaul R;Rini JM;Nixon DF;Ostrowski MA
通讯作者：
Ostrowski MA