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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Tharaux, P-L; Bukoski, RC; Rocha, PN; Crowley, SD; Ruiz, P; Nataraj, C; Howell, DN; Kaibuchi, K; Spurney, RF; Coffman, TM

Published Date

  • July 1, 2003

Published In

Volume / Issue

  • 171 / 1

Start / End Page

  • 96 - 105

PubMed ID

  • 12816987

Pubmed Central ID

  • 12816987

International Standard Serial Number (ISSN)

  • 0022-1767

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.171.1.96

Language

  • eng

Conference Location

  • United States