beta Cells cannot directly prime diabetogenic CD8 T cells in nonobese diabetic mice

de Jersey, J; Snelgrove, SL; Palmer, SE; Teteris, SA; Mullbacher, A; Miller, JFAP; Slattery, RM

Author(s): de Jersey, J; Snelgrove, SL; Palmer, SE; Teteris, SA; Mullbacher, A; Miller, JFAP; Slattery, RM;
Details: Publication Year 2007-01-23,Volume 104,Issue #4,Page 1295-1300
Journal Title: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Publication Type: Journal Article
Abstract: Type 1 diabetes (T1D) is caused by the destruction of insulin-producing islet ss cells. CD8 T cells are prevalent in the islets of T1D patients and are the major effectors of 13 cell destruction in nonobese diabetic (NOD) mice. In addition to their critical involvement in the late stages of diabetes, CD8 T cells are implicated in the initiation of disease. NOD mice, in which the ss(2)-Microglobulin gene has been inactivated by gene targeting (NOD.ss M-2(-/-)), have a deficiency in CD8 T cells and do not develop insulitis, which suggests that CD8 T cells are required for the initiation of T1D. However, neither in humans nor in NOD mice have the immunological requirements for diabetogenic CD8 T cells been precisely defined. In particular, it is not known in which cell type IVIHIC class I expression is required for recruitment and activation of CD8 T cells. Here we have generated transgenic NOD mice, which lack MHC class I on mature professional antigen-presenting cells (pAPCs). These "class I APC-bald" mice developed periislet insulitis but not invasive intraislet insulitis, and they never became diabetic. Recruitment to the islet milieu does not therefore require cognate interaction between CD8 T cells and MHC class I on mature pAPCs. Conversely, such an interaction is critically essential to allow the crucial shift from periislet insulitis to invasive insulitis. Importantly, our findings demonstrate unequivocally that CD8 T cells cannot be primed to become diabetogenic by islet ss cells alone.
Publisher: NATL ACAD SCIENCES
Keywords: MHC CLASS-I; DENDRITIC CELLS; NOD MICE; INSULITIS; ANTIGENS; GENE; AUTOANTIGENS; EXPRESSION; INITIATION; VIVO
Publisher's Version: https://doi.org/10.1073/pnas.0610057104
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2007-01-23 12:00:00