Rho Kinase Promotes Alloimmune Responses by Regulating the Proliferation and Structure of T Cells - Inserm - Institut national de la santé et de la recherche médicale Access content directly
Journal Articles Journal of Immunology Year : 2003

Rho Kinase Promotes Alloimmune Responses by Regulating the Proliferation and Structure of T Cells

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.
Fichier principal
Vignette du fichier
96.full.pdf (976.8 Ko) Télécharger le fichier

Dates and versions

inserm-03788598 , version 1 (26-09-2022)

Identifiers

Cite

Pierre-Louis Tharaux, Richard Bukoski, Paulo Rocha, Steven Crowley, Phillip Ruiz, et al.. Rho Kinase Promotes Alloimmune Responses by Regulating the Proliferation and Structure of T Cells. Journal of Immunology, 2003, 171 (1), pp.96-105. ⟨10.4049/jimmunol.171.1.96⟩. ⟨inserm-03788598⟩

Collections

INSERM
5 View
7 Download

Altmetric

Share

Gmail Facebook X LinkedIn More