AUTOIMMUNITY CAUSED BY IGNORANT CD8(+) T-CELLS IS TRANSIENT AND DEPENDS ON AVIDITY
- Author(s)
- Heath, WR; Karamalis, F; DONOGHUE, J; Miller, JFAP;
- Details
- Publication Year 1995-09-01,Volume 155,Issue #5,Page 2339-2349
- Journal Title
- JOURNAL OF IMMUNOLOGY
- Publication Type
- Journal Article
- Abstract
- RIP-K-b mice, which express H-2K(b) (K-b) molecules on their pancreatic beta cells, were used to examine the requirements for induction of autoimmune diabetes caused by CD8(+) T cells. Previous studies showed that when these mice were crossed to mice expressing a K-b-specific TCR transgene, those CD8(+) cells expressing the highest density of the transgenic TCR (presumably the highest avidity cells) were deleted intrathymically due to aberrant expression of K-b at this site. The remaining low avidity cells ignored K-b-bearing beta cells, even after priming, but were able to cause autoimmune diabetes when supplied with IL-2. To examine the properties of high avidity autoreactive CD8(+) T cells, the thymic compartment of RIP-K-b mice was replaced with normal tissue to enable the maturation of CD8(+) cells expressing the highest density of the transgenic TCR. These high avidity cells generally ignored K-b-expressing beta cells, but became autoaggressive after priming. Importantly, analysis of islet infiltration by CD8(+) T cells revealed the presence of infiltrating cells in all mice examined within 3 wk of priming, but such infiltration was not usually apparent at later time points in some cases, multiple primings were necessary for full development of autoimmunity. This implied that beta cells could act as transient targets for CD8(+) T cell attack but could not sustain the stimulation of primed CD8(+) cells. These studies indicate that the duration of the priming stimulus and the avidity of the autoreactive CD8(+) cells profoundly influence the severity of autoimmune disease.
- Publisher
- AMER ASSOC IMMUNOLOGISTS
- Keywords
- RECEPTOR TRANSGENIC MICE; CLASS-I; HISTOCOMPATIBILITY MOLECULES; VIRUS-INFECTION; ALPHA-CHAINS; TOLERANCE; EXPRESSION; INDUCTION; CONSEQUENCE; LYMPHOCYTES
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Creation Date: 1995-09-01 12:00:00