例如:"lncRNA", "apoptosis", "WRKY"

Increased attrition of memory T cells during sepsis requires 2B4.

JCI Insight. 2019 May 02;4(9). eCollection 2019 May 02
Jianfeng Xie 1 , Ching-Wen Chen 1 , Yini Sun 1 , Sonia J Laurie 1 , Wenxiao Zhang 1 , Shunsuke Otani 1 , Gregory S Martin 2 , Craig M Coopersmith 3 , Mandy L Ford 4
Jianfeng Xie 1 , Ching-Wen Chen 1 , Yini Sun 1 , Sonia J Laurie 1 , Wenxiao Zhang 1 , Shunsuke Otani 1 , Gregory S Martin 2 , Craig M Coopersmith 3 , Mandy L Ford 4
+ et al

[No authors listed]

Author information
  • 1 Department of Surgery, and.
  • 2 Division of Pulmonary, Allergy, Critical Care and Sleep, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
  • 3 Emory Critical Care Center, Department of Surgery, and.
  • 4 Emory Transplant Center, Division of Transplantation, Department of Surgery, Emory University School of Medicine, Atlanta, Georgia, USA.

摘要


Recent seminal studies have revealed that laboratory mice differ from adult humans with regard to the frequency, number, and distribution of memory T cells. Because our data show that memory T cells are more susceptible to sepsis-induced death than naive T cells, in this study we developed a model in which mice possess a memory T cell compartment more similar to that of adult humans, to better study immune responses during sepsis in the more physiologically relevant context of high frequencies of memory T cells. Using this model, we found that CD44hi memory T cells significantly upregulated the coinhibitory molecule 2B4 during sepsis, and 2B4+ memory T cells coexpressed markers of both activation and exhaustion. Genetic deficiency in 2B4 resulted in decreased mortality during sepsis. Mechanistically, this decreased mortality was associated with reduced caspase-3/7+ apoptotic T cells in 2B4-/- relative to WT, septic hosts. These results were corroborated by analysis of PBMCs isolated from human patients with sepsis, which showed increased frequencies of caspase-3/7+ apoptotic cells among 2B4+ relative to 2B4- T cells. Thus, 2B4 plays a critical role in sepsis-induced apoptosis in both murine memory T cells and those isolated from human patients with sepsis.

KEYWORDS: Immunology, Infectious disease, T cells