Analysis of thymocyte development reveals that the GTPase RhoA is a positive regulator of T cell receptor responses in vivo

Isabelle Corre, Manuel Gomez, Susina Vielkind, Doreen A. Cantrell (Lead / Corresponding author)

    Research output: Contribution to journalArticle

    53 Citations (Scopus)

    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 languageEnglish
    Pages (from-to)903-914
    Number of pages12
    JournalJournal of Experimental Medicine
    Volume194
    Issue number7
    DOIs
    Publication statusPublished - 1 Oct 2001

    Keywords

    • Antigen receptor
    • Pre-T cell receptor
    • Rac-1
    • RhoA
    • Vav-1

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