Increased attrition of memory T cells during sepsis requires 2B4.
JCI INSIGHT(2019)
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 CD44(hi) 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.
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关键词
Immunology,Infectious disease,T cells
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