First Author | Wang C | Year | 2010 |
Journal | J Immunol | Volume | 185 |
Issue | 12 | Pages | 7487-97 |
PubMed ID | 21076065 | Mgi Jnum | J:167468 |
Mgi Id | MGI:4868322 | Doi | 10.4049/jimmunol.1001424 |
Citation | Wang C, et al. (2010) Actin-bundling protein L-plastin regulates T cell activation. J Immunol 185(12):7487-97 |
abstractText | 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. |