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A role for the B7-1/B7-2:CD28/CTLA-4 pathway during negative selection.
Janet E Buhlmann1, Sheryl Krevsky Elkin, Arlene H Sharpe
1Department of Pathology, Immunology Research Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|May 22, 2003
Summary
This study reveals that B7-1 and B7-2 costimulatory molecules are crucial for negative selection of T cells. CD28 and CTLA-4 have opposing roles in thymic development, shaping the T cell repertoire.
Area of Science:
- Immunology
- T cell biology
- Molecular immunology
Background:
- Costimulation is vital for naive T cell activation.
- The role of costimulation in T cell negative selection is debated.
Purpose of the Study:
- To investigate the role of B7-1 and B7-2 costimulatory molecules in T cell negative selection.
- To elucidate the functions of CD28 and CTLA-4 in thymic T cell development.
Main Methods:
- Utilized knockout mice lacking B7-1 and/or B7-2 to study thymocyte deletion.
- Employed CD28-deficient and CD28/CTLA-4-double-deficient mice models.
- Analyzed T cell selection processes in vivo.
Main Results:
- Identified essential roles for both B7-1 and B7-2 in negative selection.
- Demonstrated that CD28 or an alternative coreceptor mediates B7-dependent negative selection signals.
- Showed that CTLA-4 inhibits selection, opposing CD28's function.
Conclusions:
- B7-1/B7-2-dependent signals are critical for shaping the T cell repertoire during thymic development.
- CD28 and CTLA-4 exhibit antagonistic functions in thymic selection.
- The findings clarify the complex interplay of costimulatory molecules in establishing immune tolerance.