Increased attrition of memory T cells during sepsis requires 2B4.
JCI Insight
; 4(9)2019 05 02.
Article
in En
| MEDLINE
| ID: mdl-31045575
ABSTRACT
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
T-Lymphocytes
/
Sepsis
/
Signaling Lymphocytic Activation Molecule Family
/
Immunologic Memory
Limits:
Adult
/
Animals
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
JCI Insight
Year:
2019
Type:
Article