Pancreatic expression of B7 co-stimulatory molecules in the non-obese diabetic mouse
- Author(s)
- Stephens, LA; Kay, TWH;
- Details
- Publication Year 1995-12,Volume 7,Issue #12,Page 1885-1895
- Journal Title
- INTERNATIONAL IMMUNOLOGY
- Publication Type
- Journal Article
- Abstract
- Expression of the co-stimulatory molecule B7-1 (CD80) on pancreatic beta cells can overcome peripheral T cell tolerance in transgenic models of autoimmune disease. This study aimed to determine if aberrant B7-1 or B7-2 (CD86) expression on pancreatic beta cells is involved in the pathogenesis of autoimmune diabetes in non-obese diabetic (NOD) mice. Immunohistochemical analysis of NOD pancreas sections revealed no evidence of B7-1 or B7-2 expression on pancreatic beta cells at any stage prior to the onset of either spontaneously arising or cyclophosphamide-accelerated diabetes. Likewise, the NOD-derived NIT-1 beta cell line did not express surface B7 or B7-1 mRNA either constitutively or following exposure to IFN-gamma and TNF-alpha, two cytokines known to be present in the insulitis lesion of NOD mice, or cAMP which can induce B7-1 expression on B cells. Both B7-1 and B7-2 were, however, highly expressed on the majority of islet-infiltrating inflammatory cells in NOD mice between days 7 and 12 after the administration of cyclophosphamide which results in accelerated beta cell destruction. Likewise B7-1 and B7-2 were extensively expressed on islet-infiltrating cells present at the time of diabetes onset in NOD SCID mice with adoptively transferred diabetes. By immunohistochemisty and flow cytometry, it was determined that the phenotype of B7(+) cells in the pancreas of NOD mice 9 days after cyclophosphamide included a mixture of macrophages and both CD4(+) and CD8(+) T cells. B7-2 was also expressed on islet-infiltrating cells in the spontaneously occurring diabetes of female NOD mice, but the levels of B7-1 expression were low in comparison with the accelerated models of diabetes. RIP-IL-2 transgenic mice, which have extensive islet infiltration but no autoimmune beta cell destruction, also had virtually no B7-1 expression and a minority of B7-2-expressing inflammatory cells. Thus, the activation of beta cell-specific T cells in NOD mice does not appear to be a result of aberrant expression of B7 on the beta cells. Expression of B7-1 and B7-2 on islet-infiltrating cells is, however, associated with autoimmune beta cell destruction, suggesting a role for the B7-CD28 interaction in this process.
- Publisher
- OXFORD UNIV PRESS UNITED KINGDOM
- Keywords
- T-CELL ACTIVATION; MAJOR COSTIMULATORY MOLECULE; CTLA-4 COUNTER-RECEPTOR; LYMPHOCYTES-T; FUNCTIONAL EXPRESSION; INTERFERON-GAMMA; TRANSGENIC MICE; CD28; ANTIGEN; LIGAND
- Publisher's Version
- https://doi.org/10.1093/intimm/7.12.1885
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 1995-12-01 12:00:00