Actin-Bundling Protein L-Plastin Regulates T Cell Activation

作者：Wang Chen; Morley Sharon Celeste; Donermeyer David; Peng Ivan; Lee Wyne P; Devoss Jason; Danilenko Dimitry M; Lin Zhonghua; Zhang Juan; Zhou Jie; Allen Paul M^*; Brown Eric J

来源：The Journal of Immunology, 2010, 185(12): 7487-7497.

DOI：10.4049/jimmunol.1001424

Engagement of TCRs induces actin rearrangements, which are critical for T cell activation. T cell responses require new actin polymerization, but the significance of higher-order actin structures, such as microfilament bundles, is unknown. To determine the role of the actin-bundling protein leukocyte-plastin (L-plastin; LPL) in this process, T cells from LPL(-/-) mice were studied. LPL(-/-) T cells were markedly defective in TCR-mediated cytokine production and proliferation. LPL(-/-) T cells also spread inefficiently on surfaces with immobilized TCR ligands and formed smaller immunological synapses with APCs, likely due to defective formation of lamellipodia. LPL(-/-) mice showed delayed rejection of skin allografts after release from immunosuppression. Moreover, LPL(-/-) mice developed much less severe neurologic symptoms in experimental autoimmune encephalomyelitis, which correlated with impaired T cell responses to Ag, manifested by reduced proliferation and production of IFN-gamma and IL-17. Thus, LPL-dependent actin bundling facilitates the formation of lamellipodia and normal immunological synapses and thereby enables T cell activation. The Journal of Immunology, 2010, 185: 7487-7497.

• 出版日期2010-12-15