Abstract
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-γ and IL-17. Thus, LPL-dependent actin bundling facilitates the formation of lamellipodia and normal immunological synapses and thereby enables T cell activation.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Actins / genetics
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Actins / immunology
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Actins / metabolism
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Animals
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Antigens / genetics
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Antigens / immunology
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Antigens / metabolism
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Cell Proliferation
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Cytoskeletal Proteins
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Encephalomyelitis, Autoimmune, Experimental / genetics
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Encephalomyelitis, Autoimmune, Experimental / immunology
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Encephalomyelitis, Autoimmune, Experimental / metabolism
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Graft Rejection / genetics
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Graft Rejection / immunology
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Graft Rejection / metabolism
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Immunological Synapses / genetics
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Immunological Synapses / immunology*
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Immunological Synapses / metabolism
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Interferon-gamma / genetics
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Interferon-gamma / immunology
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Interferon-gamma / metabolism
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Interleukin-17 / genetics
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Interleukin-17 / immunology
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Interleukin-17 / metabolism
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Lymphocyte Activation / genetics
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Lymphocyte Activation / immunology*
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Mice
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Mice, Inbred BALB C
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Mice, Knockout
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Microfilament Proteins
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Phosphoproteins / genetics
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Phosphoproteins / immunology*
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Phosphoproteins / metabolism
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Pseudopodia / genetics
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Pseudopodia / immunology
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Pseudopodia / metabolism
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Receptors, Antigen, T-Cell / genetics
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Receptors, Antigen, T-Cell / immunology
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Receptors, Antigen, T-Cell / metabolism
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Skin Transplantation / immunology
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T-Lymphocytes / immunology*
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T-Lymphocytes / metabolism
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Transplantation, Homologous
Substances
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Actins
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Antigens
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Cytoskeletal Proteins
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Interleukin-17
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Microfilament Proteins
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Phosphoproteins
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Receptors, Antigen, T-Cell
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Lcp1 protein, mouse
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Interferon-gamma