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Mixed signature of activation and dysfunction allows human decidual CD8 + T cells to provide both tolerance and immunity.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2018 Jan 09; Vol. 115 (2), pp. 385-390. Date of Electronic Publication: 2017 Dec 19. - Publication Year :
- 2018
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Abstract
- Understanding how decidual CD8 <superscript>+</superscript> T cell (CD8 <superscript>+</superscript> 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 <superscript>+</superscript> 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 <superscript>+</superscript> dT effector responses to maintain tolerance to fetal antigens. However, CD8 <superscript>+</superscript> dT degranulated, proliferated, and produced IFN-γ, TNF-α, perforin, and granzymes upon in vitro stimulation, demonstrating that CD8 <superscript>+</superscript> dT are not permanently suppressed and retain the capacity to respond to proinflammatory events, such as infections. The balance between transient dysfunction of CD8 <superscript>+</superscript> 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.<br />Competing Interests: The authors declare no conflict of interest.
- Subjects :
- CD8-Positive T-Lymphocytes immunology
Cytomegalovirus immunology
Cytomegalovirus physiology
Cytomegalovirus Infections genetics
Cytomegalovirus Infections immunology
Cytomegalovirus Infections virology
Female
Granzymes genetics
Granzymes metabolism
Humans
Immune Tolerance immunology
Lymphocyte Activation genetics
Lymphocyte Activation immunology
Perforin genetics
Perforin metabolism
Time Factors
CD8-Positive T-Lymphocytes metabolism
Decidua metabolism
Gene Expression Profiling methods
Immune Tolerance genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 115
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 29259116
- Full Text :
- https://doi.org/10.1073/pnas.1713957115