A key role for ICAM-I in generating effector cells mediating inflammatory responses
- Author(s)
- Camacho, SA; Heath, WR; Carbone, FR; Sarvetnick, N; LeBon, A; Karlsson, L; Peterson, PA; Webb, SR;
- Details
- Publication Year 2001-06,Volume 2,Issue #6,Page 523-529
- Journal Title
- NATURE IMMUNOLOGY
- Publication Type
- Journal Article
- Abstract
- We investigated how the accessory molecule interactions encountered during T cell priming influence T cell-mediated destruction of insulin-producing beta cells and lead to type I 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 beta 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.
- Publisher
- NATURE AMERICA INC
- Keywords
- INTERCELLULAR-ADHESION MOLECULE-1; CD4(+) T-CELLS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; DEPENDENT DIABETES-MELLITUS; COSTIMULATORY MOLECULES; INDUCED ARTHRITIS; LYMPHOCYTES-T; ACTIVATION; CD28; CHEMOKINES
- Publisher's Version
- https://doi.org/10.1038/88720
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2001-06-01 12:00:00