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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Lingenheld, Elizabeth G. Jellison, Evan R. Zu, Li Turner, Michael J. Blair, David A. Lefrançois, Leo Puddington, Lynn |
| Description | Author Affiliation: Jellison ER ( Department of Immunology, University of Connecticut Health Center, Farmington, CT 06030-1319, USA.); |
| 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. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 52 |
| Volume Number | 109 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2012-12-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | CD8-Positive T-Lymphocytes Immunology Immune Tolerance Immunologic Memory Animals Antigens, CD8 Autoantigens Cytology Lymphocyte Activation Lymphoid Tissue Mice Mice, Transgenic Research Support, N.I.H., Extramural Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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