期刊
JOURNAL OF LEUKOCYTE BIOLOGY
卷 109, 期 3, 页码 645-656出版社
OXFORD UNIV PRESS
DOI: 10.1002/JLB.4A0520-122R
关键词
trauma; memory; CyTOF; danger; MHC-II; injury
资金
- U.S. National Institutes of Health [5R01 AI092905-05]
- Brigham and Women's Hospital-Biomedical Research Institute
- NIH [T32 GM 103702-5]
- Department of Defense [W81XWH-16-1-0464]
CD4+ regulatory T cells (Tregs) are acutely activated by traumatic injury, similar to memory T cells. The study found that injury activates a memory-like Treg subpopulation, and that Treg activation by injury is partially dependent on TCR signaling by an MHC class II dependent mechanism. This suggests a complex regulatory role for Tregs in response to trauma.
CD4+ regulatory T cells (Tregs) are acutely activated by traumatic injury, which suggests that they may react to injury with similar kinetics as memory T cells. Here, we used a mouse burn trauma model to screen for memory-like T cell responses to injury by transferring T cells from sham or burn CD45.1 mice into CD45.2 mice and performing secondary injuries in recipient mice. Among all T cell subsets that were measured, only Tregs expanded in response to secondary injury. The expanded Tregs were a CD44(high)/CD62L(low)subpopulation, markers indicative of memory T cells. CyTOF (cytometry by time-of-flight) mass cytometry was used to demonstrate that injury-expanded Tregs expressed higher levels of CD44, CTLA-4, ICOS, GITR, and Helios than Tregs from noninjured mice. Next, we tested whether a similar population of Tregs might react acutely to burn trauma. We observed that Tregs with a phenotype that matched the injury-expanded Tregs were activated by 6 h after injury. To test if Treg activation by trauma requires functional MHC class II, we measured trauma-induced Treg activation in MHC class II gene deficient (MHCII-/-) mice or in mice that were given Fab fragment of anti-MHC class II antibody to block TCR activation. Injury-induced Treg activation occurred in normal mice but only partial activation was detected in MHCII(-/-)mice or in mice that were given Fab anti-MHCII antibody. These findings demonstrate that trauma activates a memory-like Treg subpopulation and that Treg activation by injury is partially dependent on TCR signaling by an MHC class II dependent mechanism.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据