CD8 T cell ignorance or tolerance to islet antigens depends on antigen dose
- Author(s)
- Kurts, C; Sutherland, RM; Davey, G; Li, M; Lew, AM; Blanas, E; Carbone, FR; Miller, JFAP; Heath, WR;
- Details
- Publication Year 1999-10-26,Volume 96,Issue #22,Page 12703-12707
- Journal Title
- PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
- Publication Type
- Journal Article
- Abstract
- There are two major mechanisms reported to prevent the autoreactivity of islet-specific CD8(+) T cells: ignorance and tolerance. When ignorance is operative, naive autoreactive CD8(+) T cells ignore islet antigens and recirculate without causing damage, unless activated by an external stimulus. In the case of tolerance, CD8(+) T cells are deleted. Which factor(s) contributes to each particular outcome was previously unknown. Here, we demonstrate that the concentration of self antigen determines which mechanism operates. When ovalbumin (OVA) was expressed at a relatively low concentration in the pancreatic islets of transgenic mice, there was no detectable cross-presentation, and the CD8(+) T cell compartment remained ignorant of OVA. In mice expressing higher doses of OVA, cross-presentation was detectable and led to peripheral deletion of OVA-specific CD8(+) T cells. When cross-presentation was prevented by reconstituting the bone marrow compartment with cells incapable of presenting OVA, deletional tolerance was converted to ignorance. Thus, the immune system uses two strategies to avoid CD8(+) T cell-mediated autoimmunity: for high dose antigens, it deletes autoreactive T cells, whereas for lower dose antigens, it relies on ignorance.
- Publisher
- NATL ACAD SCIENCES
- Keywords
- RESTRICTED CROSS-PRESENTATION; SELF-ANTIGENS; VIRUS-INFECTION; INDUCTION; DELETION
- Publisher's Version
- https://doi.org/10.1073/pnas.96.22.12703
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 1999-10-26 12:00:00