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Isolation of Peritoneum-derived Mast Cells and Their Functional Characterization with Ca2+-imaging and Degranulation Assays
Published on: July 4, 2018
A key role for ICAM-1 in generating effector cells mediating inflammatory responses
S A Camacho1, W R Heath, F R Carbone
1Department of Immunology, IMM4, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Nature Immunology
|May 29, 2001
Summary
Interactions between T cells and antigen-presenting cells during T cell priming dictate autoimmune responses. Co-engagement of ICAM-1 with B7-1 promotes beta cell destruction and type 1 diabetes development.
Area of Science:
- Immunology
- Endocrinology
- Autoimmunity
Background:
- Type 1 diabetes involves autoimmune destruction of insulin-producing beta cells.
- T cell activation and differentiation are critical in initiating autoimmune responses.
Purpose of the Study:
- To investigate how accessory molecule interactions during T cell priming influence T cell-mediated beta cell destruction.
- To determine the role of specific co-stimulatory molecules in the development of type 1 diabetes.
Main Methods:
- T cell receptor (TCR)-transgenic CD4+ T cells were primed in vitro.
- Primed T cells were adoptively transferred into transgenic recipients expressing membrane ovalbumin under the rat insulin promoter (RIP-mOVA).
- Antigen-presenting cells (APCs) were manipulated for expression of B7-1 and intracellular adhesion molecule 1 (ICAM-1) during priming.
Main Results:
- Priming with B7-1 alone generated effector cells that migrated to the pancreas but did not cause diabetes.
- Priming with both B7-1 and ICAM-1 led to significant beta cell destruction and rapid diabetes onset.
- Pathogenic T cells produced macrophage-attracting chemokines CCL3 and CCL4.
Conclusions:
- Interaction of lymphocyte function-associated antigen 1 (LFA-1) with ICAM-1 during T cell priming alters T effector function.
- ICAM-1 co-stimulation during priming is crucial for inducing T cell pathogenicity and autoimmune responses against beta cells.
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