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.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
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.
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U2 - 10.4049/jimmunol.171.1.96
DO - 10.4049/jimmunol.171.1.96
M3 - Article
C2 - 12816987
AN - SCOPUS:0038206719
SN - 0022-1767
VL - 171
SP - 96
EP - 105
JO - Journal of Immunology
JF - Journal of Immunology
IS - 1
ER -