Tissue destruction caused by cytotoxic T lymphocytes induces deletional tolerance
- Author(s)
- Parish, IA; Waithman, J; Davey, GM; Belz, GT; Mintern, JD; Kurts, C; Sutherland, RM; Carbone, FR; Heath, WR;
- Details
- Publication Year 2009-03-10,Volume 106,Issue #10,Page 3901-3906
- Journal Title
- PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
- Publication Type
- Journal Article
- Abstract
- Autoimmune diseases tend to be chronic and progressive, but how these responses are sustained is not clear. One cell type that might contribute to autoimmunity is the cytotoxic T lymphocyte (CTL), which, as a consequence of causing tissue destruction and production of cytokines, could provide a sustained supply of antigen and inflammatory signals for dendritic cells to maintain immune stimulation. Here we examined whether such CTL-mediated tissue damage alone could provide antigen in the right context to recruit immune effectors and sustain autoimmunity. We show that while CTL-mediated tissue damage caused the release of self-antigens that stimulated the proliferation of naive autoreactive CD8(+) T cells, such responses failed to precipitate disease and, instead, led to deletional tolerance. These findings indicate that despite the capacity of CTLs to produce inflammatory cytokines and to cause tissue damage, their responses are not sustaining, but instead favor induction of self-tolerance.
- Publisher
- NATL ACAD SCIENCES
- Keywords
- DENDRITIC CELL MATURATION; TOLL-LIKE RECEPTOR-4; IN-VIVO; CROSS-PRESENTATION; APOPTOTIC CELLS; ISLET ANTIGENS; SELF-ANTIGENS; CUTTING EDGE; DYING CELLS; INDUCTION
- Publisher's Version
- https://doi.org/10.1073/pnas.0810427106
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2009-03-10 12:00:00