The GTPase Rac-1 controls cell fate in the thymus by diverting thymocytes from positive to negative selection.
The positive selection of CD4 or CD8 single-positive mature peripheral T lymphocytes and the deletion of self-reactive cells are crucial for central tolerance in the peripheral immune system. Previously, the guanine nucleotide binding protein Rac-1 has been shown to control pre-T cell development. The present report now describes the actions of Rac-1 in thymocyte selection. The study reveals that this molecule has the striking and unique ability to efficiently divert cells from positive selection into a pathway of negative selection and deletion. The ability of Rac-1 to switch thymocytes from a destiny of positive to negative selection identifies this molecule as a critical regulator of the developmental processes in T cells that are essential for immune homeostasis.
Gomez
M
M
Imperial Cancer Research Fund, Lymphocyte Activation Laboratory, 44 Lincoln's Inn Fields, London, WC2A 3PX, United Kingdom.
Kioussis
D
D
Cantrell
D A
DA
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D015398:Signal Transduction / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology*; D020830:rac1 GTP-Binding Protein / Q000276:immunology*
D020830:rac1 GTP-Binding Protein