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- Title
A key role for ICAM-1 in generating effector cells mediating inflammatory responses.
- Authors
Camacho, Stephanie A.; Heath, William R.; Carbone, Francis R.; Sarvetnick, Nora; LeBon, Agnes; Karlsson, Lars; Peterson, Per A.; Webb, Susan R.
- Abstract
We investigated how the accessory molecule interactions encountered during T cell priming influence T cell?mediated destruction of insulin-producing β cells and lead to type 1 diabetes. T cell receptor (TCR)-transgenic CD4+ T cells were primed under controlled conditions in vitro before being adoptively transferred into transgenic recipients expressing membrane ovalbumin under the control of the rat insulin promoter (RIP-mOVA). During priming, antigen-presenting cell expression of B7-1 without intracellular adhesion molecule 1 (ICAM-1) led to the generation of effector cells that migrated to the pancreata of RIP-mOVA recipients but did not cause diabetes. In contrast, when T cells were primed with APCs expressing both B7-1 and ICAM-1, pronounced destruction of β cells and a rapid onset of diabetes were observed. Pathogenicity was associated with T cell production of the macrophage-attracting chemokines CCL3 and CCL4. Thus, interactions of lymphocyte function?associated antigen 1 with ICAM-1 during priming induce both qualitative and quantitative alterations in T effector function and induce potentially autodestructive responses.
- Subjects
T cells; PANCREATIC beta cells; DIABETES; INSULIN
- Publication
Nature Immunology, 2001, Vol 2, Issue 6, p523
- ISSN
1529-2908
- Publication type
Article
- DOI
10.1038/88720