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CD28-B7 interactions are not required for intrathymic clonal deletion
L A Jones1, D J Izon, J D Nieland
1Division of Immunology, Netherlands Cancer Institute, Amsterdam.
International Immunology
|May 1, 1993
Summary
The CD28-B7 costimulation pathway is crucial for T cell activation by superantigens. However, this pathway is not involved in intrathymic clonal deletion, a key process in immune tolerance.
Area of Science:
- Immunology
- Cellular Immunology
- T cell biology
Background:
- T cell activation requires TCR-CD3 stimulation and a costimulatory signal.
- The CD28-B7 interaction provides a critical costimulatory signal between T cells and antigen-presenting cells.
- Superantigens activate T cells, and their role in T cell selection processes is incompletely understood.
Purpose of the Study:
- To investigate the role of the CD28-B7 costimulatory pathway in superantigen-mediated T cell activation.
- To determine the involvement of the CD28-B7 interaction in intrathymic negative selection (clonal deletion).
Main Methods:
- Blocking B7 molecules using a high-affinity soluble ligand, CTLA4Ig.
- Assessing T cell activation in vitro using superantigens.
- Evaluating intrathymic clonal deletion in vivo and in fetal thymic organ cultures.
Main Results:
- In vitro T cell activation by both endogenous and exogenous superantigens was significantly inhibited by CTLA4Ig.
- Intrathymic clonal deletion, in vivo and in fetal thymic organ cultures, was not affected by blocking B7 molecules.
Conclusions:
- The CD28-B7 costimulation pathway is essential for superantigen-induced T cell activation.
- The CD28-B7 pathway does not play a significant role in the process of intrathymic clonal deletion.