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Distinct mechanisms mediate naïve and memory CD8 T-cell tolerance.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America . 12/26/2012, Vol. 109 Issue 52, p21438-21443. 6p. - Publication Year :
- 2012
-
Abstract
- Peripheral tolerance to developmentally regulated antigens is necessary to sustain tissue homeostasis. We have now devised an inducible and reversible system that allows interrogation of T-cell tolerance induction in endogenous naïve and memory CD8 T cells. Our data show that peripheral CD8 T-cell tolerance can be preserved through two distinct mechanisms, antigen addiction leading to anergy for naïve T cells and ignorance for memory T cells. Induction of antigen in dendritic cells resulted in substantial expansion and maintenance of endogenous antigen-specific CD8 T cells. The self-reactive cells initially exhibited effector activity but eventually became unresponsive. Upon antigen removal, the antigen-specific population waned, resulting in development of a self-specific memory subset that recalled to subsequent challenge. In striking contrast to naïve CD8 T cells, preexisting antigen-specific memory CD8 T cells failed to expand after antigen induction and essentially ignored the antigen despite widespread expression by dendritic cells. The inclusion of inflammatory signals partially overcame memory CD8 T-cell ignorance of self-antigen. Thus, peripheral CD8 T-cell tolerance for naïve CD8 T cells depended on the continuous presence of antigen, whereas memory CD8 T cells were prohibited from autoreactivity in the absence of inflammation. [ABSTRACT FROM AUTHOR]
- Subjects :
- *T cells
*ANTIGENS
*HOMEOSTASIS
*DENDRITIC cells
*TISSUES
*INFLAMMATION
Subjects
Details
- Language :
- English
- ISSN :
- 00278424
- Volume :
- 109
- Issue :
- 52
- Database :
- Academic Search Index
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 84557678
- Full Text :
- https://doi.org/10.1073/pnas.1217409110