Abstract
Loss of function of the guanine nucleotide binding protein RhoA blocks pre-T cell differentiation and survival indicating that this GTPase is a critical signaling molecule during early thymocyte development. Previous work has shown that the Rho family GTPase Rac-1 can initiate changes in actin dynamics necessary and sufficient for pre-T cell development. The present data now show that Rac-1 actions in pre-T cells require Rho function but that RhoA cannot substitute for Rac-1 and induce the actin cytoskeletal changes necessary for pre-T cell development. Activation of Rho is thus not sufficient to induce pre-T cell differentiation or survival in the absence of the pre-T cell receptor (TCR). The failure of RhoA activation to impact on pre-TCR-mediated signaling was in marked contrast to its actions on T cell responses mediated by the mature TCR α/β complex. Cells expressing active RhoA were thus hyperresponsive in the context of TCR-induced proliferation in vitro and in vivo showed augmented positive selection of thymocytes expressing defined TCR complexes. This reveals that RhoA function is not only important for pre-T cells but also plays a role in determining the fate of mature T cells.
Original language | English |
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Pages (from-to) | 903-914 |
Number of pages | 12 |
Journal | Journal of Experimental Medicine |
Volume | 194 |
Issue number | 7 |
DOIs | |
Publication status | Published - 1 Oct 2001 |
Keywords
- Antigen receptor
- Pre-T cell receptor
- Rac-1
- RhoA
- Vav-1
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology