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Original Article |
Correspondence to: Doreen A. Cantrell, Lymphocyte Activation Laboratory, Imperial Cancer Research Fund, 44 Lincoln Inn Fields, London, WC2A 3PX, UK. Tel:44-020-7269-3307 Fax:44-020-7269-3479 E-mail:d.cantrell{at}icrf.icnet.uk.
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 
/ß 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.
Key Words: Rac-1, Vav-1, RhoA, antigen receptor, pre-T cell receptor
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