Comparison of influenza and SIV specific CD8 T cell responses in macaques.
Comparison of influenza and SIV specific CD8 T cell responses in macaques.
复制标题
DOI：
10.1371/journal.pone.0032431
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Sexton A
中科院分区：
文献类型：
--
作者：
Jegaskanda S;Reece JC;De Rose R;Stambas J;Sullivan L;Brooks AG;Kent SJ;Sexton A
猕猴是一种潜在有用的非人灵长类动物模型，用于比较对急性病毒病原体（如流感病毒）的记忆T细胞免疫和对慢性病毒病原体（如SIV）的效应T细胞应答。然而，研究猕猴模型中流感CD 8 + T细胞应答的免疫试剂是有限的。我们最近开发了猪尾猕猴（Macaca nemestrina）的流感-SIV疫苗接种模型，并使用该模型研究了39只表达常见Mane-A*10+（Mane-A01*084）MHC-I等位基因的猪尾猕猴中流感特异性和SIV特异性CD 8 + T细胞。为了进行流感和SIV应答之间的比较研究，将常见的流感核蛋白特异性CD 8 + T细胞应答映射到最小表位（称为RA 9），MHC限制性映射到Mane-A*10和开发用于研究该应答的MHC四聚体。流感特异性记忆性CD 8 + T细胞应答在众多效应分子（CD 107 a、IFN-γ、TNF-α、MIP-1β和IL-2）表达方面保持高度功能性，并且即使在SIV感染的情况下也显示出高亲和力。相反，在活动性SIV感染后数周内，与流感特异性CD 8 + T细胞相比，SIV特异性CD 8+效应T细胞表达较少的细胞因子/脱粒标志物，并且具有较低的亲合力。此外，流感特异性记忆CD 8 T细胞应答在感染SIV后保持耗竭标志物程序性死亡标志物-I（PD-1）和共刺激分子CD 28的稳定表达。这与SIV感染后的效应SIV特异性CD 8 + T细胞形成对比，后者表达显著更高量的PD-1和更低量的CD 28。我们的研究结果表明，维持功能更强的CD 8 + T细胞应答的策略可能有助于控制HIV疾病。
Macaques are a potentially useful non-human primate model to compare memory T-cell immunity to acute virus pathogens such as influenza virus and effector T-cell responses to chronic viral pathogens such as SIV. However, immunological reagents to study influenza CD8+ T-cell responses in the macaque model are limited. We recently developed an influenza-SIV vaccination model of pigtail macaques (Macaca nemestrina) and used this to study both influenza-specific and SIV-specific CD8+ T-cells in 39 pigtail macaques expressing the common Mane-A*10+ (Mane-A01*084) MHC-I allele. To perform comparative studies between influenza and SIV responses a common influenza nucleoprotein-specific CD8+ T-cell response was mapped to a minimal epitope (termed RA9), MHC-restricted to Mane-A*10 and an MHC tetramer developed to study this response. Influenza-specific memory CD8+ T-cell response maintained a highly functional profile in terms of multitude of effector molecule expression (CD107a, IFN-γ, TNF-α, MIP-1β and IL-2) and showed high avidity even in the setting of SIV infection. In contrast, within weeks following active SIV infection, SIV-specific CD8+ effector T-cells expressed fewer cytokines/degranulation markers and had a lower avidity compared to influenza specific CD8+ T-cells. Further, the influenza specific memory CD8 T-cell response retained stable expression of the exhaustion marker programmed death-marker-1 (PD-1) and co-stimulatory molecule CD28 following infection with SIV. This contrasted with the effector SIV-specific CD8+ T-cells following SIV infection which expressed significantly higher amounts of PD-1 and lower amounts of CD28. Our results suggest that strategies to maintain a more functional CD8+ T-cell response, profile may assist in controlling HIV disease.
登录
查看更多内容
影响因子：
5.4
作者：
Andreansky, SS;Stambas, J;Doherty, PC
通讯作者：
Doherty, PC
DOI：
10.1084/jem.20070784
发表时间：
2007-10-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Almeida JR;Price DA;Papagno L;Arkoub ZA;Sauce D;Bornstein E;Asher TE;Samri A;Schnuriger A;Theodorou I;Costagliola D;Rouzioux C;Agut H;Marcelin AG;Douek D;Autran B;Appay V
通讯作者：
Appay V
影响因子：
5.4
作者：
Hurt, Aeron C.;Nor'e, Siti Sarah;Barr, Ian G.
通讯作者：
Barr, Ian G.
影响因子：
3.8
作者：
Gillespie, GMA;Kaul, R;Rowland-Jones, SL
通讯作者：
Rowland-Jones, SL
影响因子：
5.4
作者：
De Rose, Robert;Batten, C. Jane;Kent, Stephen J.
通讯作者：
Kent, Stephen J.