Actin-bundling protein L-plastin regulates T cell activation.

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.

• Authors: Chen Wang, Sharon Celeste Morley, David Donermeyer, Ivan Peng, Wyne P Lee, Jason Devoss, Dimitry M Danilenko, Zhonghua Lin, Juan Zhang, Jie Zhou, Paul M Allen, Eric J Brown
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 185 Issue 12 Pg. 7487-97 (Dec 15 2010) ISSN: 1550-6606 [Electronic] United States
• PMID: 21076065 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Actins
• Antigens
• Cytoskeletal Proteins
• Interleukin-17
• Microfilament Proteins
• Phosphoproteins
• Receptors, Antigen, T-Cell
• Lcp1 protein, mouse
• Interferon-gamma

Topics

• Actins (genetics, immunology, metabolism)
• Animals
• Antigens (genetics, immunology, metabolism)
• Cell Proliferation
• Cytoskeletal Proteins
• Encephalomyelitis, Autoimmune, Experimental (genetics, immunology, metabolism)
• Graft Rejection (genetics, immunology, metabolism)
• Immunological Synapses (genetics, immunology, metabolism)
• Interferon-gamma (genetics, immunology, metabolism)
• Interleukin-17 (genetics, immunology, metabolism)
• Lymphocyte Activation (genetics, immunology)
• Mice
• Mice, Inbred BALB C
• Mice, Knockout
• Microfilament Proteins
• Phosphoproteins (genetics, immunology, metabolism)
• Pseudopodia (genetics, immunology, metabolism)
• Receptors, Antigen, T-Cell (genetics, immunology, metabolism)
• Skin Transplantation (immunology)
• T-Lymphocytes (immunology, metabolism)
• Transplantation, Homologous