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 journalArticle

49 Citations (Scopus)

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

Fingerprint

rho-Associated Kinases
T-Lymphocytes
Jurkat Cells
T-Cell Antigen Receptor-CD3 Complex
Cytokines
Actomyosin
rho GTP-Binding Proteins
Cell Shape
Myosins
Actin Cytoskeleton
GTP-Binding Proteins
Cellular Immunity
Polymerization
Transfection
Signal Transduction
Phosphotransferases
Cell Proliferation
Lymphocytes
Transplants
Lipids

ASJC Scopus subject areas

  • Immunology

Cite this

Tharaux, P. L., Bukoski, R. C., Rocha, P. N., Crowley, S. D., Ruiz, P., Nataraj, C., ... Coffman, T. M. (2003). Rho kinase promotes alloimmune responses by regulating the proliferation and structure of T cells. Journal of Immunology, 171(1), 96-105.

Rho kinase promotes alloimmune responses by regulating the proliferation and structure of T cells. / Tharaux, Pierre Louis; Bukoski, Richard C.; Rocha, Paulo N.; Crowley, Steven D.; Ruiz, Phillip; Nataraj, Chandra; Howell, David N.; Kaibuchi, Kozo; Spurney, Robert F.; Coffman, Thomas M.

In: Journal of Immunology, Vol. 171, No. 1, 01.07.2003, p. 96-105.

Research output: Contribution to journalArticle

Tharaux, PL, Bukoski, RC, Rocha, PN, Crowley, SD, Ruiz, P, Nataraj, C, Howell, DN, Kaibuchi, K, Spurney, RF & Coffman, TM 2003, 'Rho kinase promotes alloimmune responses by regulating the proliferation and structure of T cells', Journal of Immunology, vol. 171, no. 1, pp. 96-105.
Tharaux PL, Bukoski RC, Rocha PN, Crowley SD, Ruiz P, Nataraj C et al. Rho kinase promotes alloimmune responses by regulating the proliferation and structure of T cells. Journal of Immunology. 2003 Jul 1;171(1):96-105.
Tharaux, Pierre Louis ; Bukoski, Richard C. ; Rocha, Paulo N. ; Crowley, Steven D. ; Ruiz, Phillip ; Nataraj, Chandra ; Howell, David N. ; Kaibuchi, Kozo ; Spurney, Robert F. ; Coffman, Thomas M. / Rho kinase promotes alloimmune responses by regulating the proliferation and structure of T cells. In: Journal of Immunology. 2003 ; Vol. 171, No. 1. pp. 96-105.
@article{dede93db432c4d158fb10e104ddd922e,
title = "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.",
author = "Tharaux, {Pierre Louis} and Bukoski, {Richard C.} and Rocha, {Paulo N.} and Crowley, {Steven D.} and Phillip Ruiz and Chandra Nataraj and Howell, {David N.} and Kozo Kaibuchi and Spurney, {Robert F.} and Coffman, {Thomas M.}",
year = "2003",
month = "7",
day = "1",
language = "English",
volume = "171",
pages = "96--105",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "1",

}

TY - JOUR

T1 - Rho kinase promotes alloimmune responses by regulating the proliferation and structure of T cells

AU - Tharaux, Pierre Louis

AU - Bukoski, Richard C.

AU - Rocha, Paulo N.

AU - Crowley, Steven D.

AU - Ruiz, Phillip

AU - Nataraj, Chandra

AU - Howell, David N.

AU - Kaibuchi, Kozo

AU - Spurney, Robert F.

AU - Coffman, Thomas M.

PY - 2003/7/1

Y1 - 2003/7/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0038206719&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0038206719&partnerID=8YFLogxK

M3 - Article

C2 - 12816987

AN - SCOPUS:0038206719

VL - 171

SP - 96

EP - 105

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 1

ER -