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Differing roles for B7 and intercellular adhesion molecule-1 in negative selection of thymocytes
H Kishimoto1, Z Cai, A Brunmark
1Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA.
The Journal of Experimental Medicine
|August 1, 1996
Summary
Two costimulatory molecules, B7-1 and intercellular adhesion molecule-1 (ICAM-1), play distinct roles in T cell negative selection. Their differential expression in the thymus may dictate the sites of T cell positive and negative selection.
Area of Science:
- Immunology
- T cell biology
- Thymic selection
Background:
- Self tolerance is maintained by eliminating high-affinity T cells via negative selection.
- Costimulatory molecules B7-1 and ICAM-1 are implicated in T cell development.
- Understanding their roles is crucial for deciphering thymic selection processes.
Purpose of the Study:
- To investigate the individual and combined roles of B7-1 and ICAM-1 in T cell negative selection.
- To determine how the differential expression of these molecules influences thymic selection sites.
Main Methods:
- Studied apoptosis of T cell receptor transgenic CD4+8+ thymocytes.
- Utilized MHC class I-transfected Drosophila cells expressing B7-1 and/or ICAM-1.
- Analyzed T cell negative selection in response to specific peptides.
Main Results:
- Coexpression of B7-1 and ICAM-1 induced strong negative selection.
- B7-1 alone augmented negative selection, while ICAM-1 alone inhibited it.
- Differential expression patterns (B7-1 in medulla, ICAM-1 throughout) suggest distinct functional roles.
Conclusions:
- B7-1 and ICAM-1 exhibit opposing functions in T cell negative selection when expressed individually.
- Their distinct distributions within the thymus likely guide positive selection in the cortex and negative selection in the medulla.
- This highlights a mechanism for spatially regulating thymic T cell selection.