细胞毒性T细胞
效应器
CD8型
生物
细胞生物学
T细胞
免疫学
免疫系统
遗传学
体外
作者
Seung-Woo Lee,Yunji Park,Aihua Song,Hilde Cheroutre,Byoung S. Kwon,Michael Croft
出处
期刊:Journal of Immunology
[The American Association of Immunologists]
日期:2006-10-01
卷期号:177 (7): 4464-4472
被引量:92
标识
DOI:10.4049/jimmunol.177.7.4464
摘要
Abstract Members of the TNFR family are thought to deliver costimulatory signals to T cells and modulate their function and survival. In this study, we compare the role of two closely related TNFR family molecules, OX40 and 4-1BB, in generating effector CD8 T cells to Ag delivered by adenovirus. OX40 and 4-1BB were both induced on responding naive CD8 T cells, but 4-1BB exhibited faster and more sustained kinetics than OX40. OX40-deficient CD8 T cells initially expanded normally; however, their accumulation and survival at late times in the primary response was significantly impaired. In contrast, 4-1BB-deficient CD8 T cells displayed hyperresponsiveness, expanding more than wild-type cells. The 4-1BB-deficient CD8 T cells also showed enhanced maturation attributes, whereas OX40-deficient CD8 T cells had multiple defects in the expression of effector cell surface markers, the synthesis of cytokines, and in cytotoxic activity. These results suggest that, in contrast to current ideas, OX40 and 4-1BB can have a clear functional dichotomy in modulating effector CD8 T cell responses. OX40 can positively regulate effector function and late accumulation/survival, whereas 4-1BB can initially operate in a negative manner to limit primary CD8 responses.
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