期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 115, 期 2, 页码 385-390出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1713957115
关键词
pregnancy; T cell exhaustion; trophoblast; cytotoxicity; placenta
资金
- National Institutes of Health [AI053330]
- March of Dimes [6-FY14-453]
- VSBfonds
- Studiefonds KeteM
- Portuguese Foundation for Science and Technology-FCT [SFRH/BD/33885/2009]
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R56AI053330, R01AI053330] Funding Source: NIH RePORTER
Understanding how decidual CD8(+) T cell (CD8(+) dT) cytotoxicity is regulated and how these cells integrate the competing needs for maternal-fetal tolerance and immunity to infection is an important research and clinical goal. Gene-expression analysis of effector-memory CD8(+) dT demonstrated a mixed transcriptional signature of T cell dysfunction, activation, and effector function. High protein expression of coinhibitory molecules PD1, CTLA4, and LAG3, accompanied by low expression of cytolytic molecules suggests that the decidual microenvironment reduces CD8(+) dT effector responses to maintain tolerance to fetal antigens. However, CD8(+) dT degranulated, proliferated, and produced IFN-gamma, TNF-alpha, perforin, and granzymes upon in vitro stimulation, demonstrating that CD8(+) dT are not permanently suppressed and retain the capacity to respond to proinflammatory events, such as infections. The balance between transient dysfunction of CD8(+) dT that are permissive of placental and fetal development, and reversal of this dysfunctional state, is crucial in understanding the etiology of pregnancy complications and prevention of congenital infections.
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