Sustained and incomplete recovery of naive CD8+ T cell precursors after sepsis contributes to impaired CD8+ T cell responses to infection.
Sustained and incomplete recovery of naive CD8+ T cell precursors after sepsis contributes to impaired CD8+ T cell responses to infection.
复制标题
DOI：
10.4049/jimmunol.1202379
复制
发表时间：
2013-03-01
期刊：
影响因子：
--
通讯作者：
Badovinac VP
中科院分区：
文献类型：
--
作者：
Condotta SA;Rai D;James BR;Griffith TS;Badovinac VP
严重脓毒症存活的患者通常表现出免疫功能受损，先天性和适应性免疫应答受损。这些脓毒症患者极易受到通常由CD 8 + T细胞控制的细胞内病原体的“继发性”感染。目前尚不清楚这种观察到的CD 8 + T细胞免疫的免疫麻痹何时以及是否恢复，并且对脓毒症对幼稚CD 8 + T细胞响应后续感染的能力的长期后果知之甚少。在这里，使用CLP小鼠脓毒症模型，我们表明脓毒症诱导幼稚CD 8 + T细胞的快速损失。然而，IL-15依赖性的数值恢复在初始脓毒性损伤后一个月观察到。数值恢复伴随着IL-15依赖性表型变化，其中相当大比例的幼稚（抗原无经验）CD 8 + T细胞显示出“记忆样”表型（CD 44 hi/CD 11 ahi）。重要的是，幼稚CD 8 + T细胞对病毒和细菌感染的应答受损在脓毒症诱导后持续数月。在脓毒症小鼠中观察到幼稚CD 8 + T细胞前体的不完全恢复，表明幼稚前体的可用性有助于原发性CD 8 + T细胞应答的持续损害。因此，脓毒症可导致可用的CD 8 + T细胞库的实质性和持久的变化，影响宿主对新感染的反应能力。
Patients who survive severe sepsis often display compromised immune function with impairment in innate and adaptive immune responses. These septic patients are highly susceptible to ‘secondary’ infections with intracellular pathogens that are usually controlled by CD8+ T-cells. It is unknown when and if this observed immunoparalysis of CD8+ T-cell immunity recovers and the long-term consequences of sepsis on the ability of naïve CD8+ T-cells to respond to subsequent infections are poorly understood. Here, using the CLP mouse model of sepsis we show that sepsis induces a rapid loss of naïve CD8+ T-cells. However, IL-15-dependent numerical recovery is observed a month after initial septic insult. Numerical recovery is accompanied by IL-15-dependent phenotypic changes where a substantial proportion of naïve (antigen-inexperienced) CD8+ T-cells display a ‘memory-like’ phenotype (CD44hi/CD11ahi). Importantly, the impairment of naïve CD8+ T-cells to respond to viral and bacterial infection was sustained for month(s) after sepsis induction. Incomplete recovery of naïve CD8+ T-cell precursors was observed in septic mice, suggesting that the availability of naïve precursors contributes to the sustained impairment in primary CD8+ T-cell responses. Thus, sepsis can result in substantial and long-lasting changes in the available CD8+ T-cell repertoire affecting the capacity of the host to respond to new infections.
登录
查看更多内容
DOI：
10.4049/jimmunol.1101180
发表时间：
2011-09-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Gurung P;Rai D;Condotta SA;Babcock JC;Badovinac VP;Griffith TS
通讯作者：
Griffith TS
DOI：
10.1084/jem.20001021
发表时间：
2002-03-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Blattman JN;Antia R;Sourdive DJ;Wang X;Kaech SM;Murali-Krishna K;Altman JD;Ahmed R
通讯作者：
Ahmed R
影响因子：
120.7
作者：
Boomer, Jonathan S.;To, Kathleen;Chang, Kathy C.;Takasu, Osamu;Osborne, Dale F.;Walton, Andrew H.;Bricker, Traci L.;Jarman, Stephen D., II;Kreisel, Daniel;Krupnick, Alexander S.;Srivastava, Anil;Swanson, Paul E.;Green, Jonathan M.;Hotchkiss, Richard S.
通讯作者：
Hotchkiss, Richard S.
影响因子：
5.5
作者：
Flohe, Stefanie B.;Agrawal, Hemant;Schade, F. Ulrich
通讯作者：
Schade, F. Ulrich
影响因子：
82.9
作者：
Badovinac, VP;Messingham, KAN;Harty, JT
通讯作者：
Harty, JT