Rho kinase promotes alloimmune responses by regulating the proliferation and structure of T cells

Pierre Louis Tharaux, Richard C. Bukoski, Paulo N. Rocha, Steven D. Crowley, Phillip Ruiz, Chandra Nataraj, David N. Howell, Kozo Kaibuchi, Robert F. Spurney, Thomas M. Coffman

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

Coordinated rearrangements of the actin-myosin cytoskeleton facilitate early and late events in T cell activation and signal transduction. As many important features of cell shape rearrangement involve small GTP-binding proteins, we examined the contribution of Rho kinase to the functions of mature T cells. Inhibitors of the Rho kinase pathway all had similar actions to inhibit the proliferation of primary lymphocyte cultures. Likewise, transfection of the human Jurkat T cell line with a dominant negative, kinase-defective mutant of Rho kinase diminished Jurkat cell proliferation. Furthermore, inhibition of Rho kinase substantially attenuated the program of cytokine gene expression that characterizes T cell activation, blocked actomyosin polymerization, and prevented aggregation of the TCR/CD3 complex colocalized with lipid rafts. These actions are relevant to immune responses in vivo, as treatment with a Rho kinase inhibitor considerably prolonged the survival of fully allogeneic heart transplants in mice and diminished intragraft expression of cytokine mRNAs. Thus, Rho GTPases acting through Rho kinase play a unique role in T cell activation during cellular immune responses by promoting structural rearrangements that are critical for T cell signaling.

Original languageEnglish (US)
Pages (from-to)96-105
Number of pages10
JournalJournal of Immunology
Volume171
Issue number1
DOIs
StatePublished - Jul 1 2003

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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