Ena/VASP protein-mediated actin polymerization contributes to naive CD8+ T cell activation and expansion by promoting T cell-APC interactions in vivo

Autor: Monique M Waldman, Jeremy T. Rahkola, Benjamin A.S. Willett, Jeffrey W. Chung, Ashton L. Sigler, Rachel S. Friedman, Ross M. Kedl, Jordan Jacobelli
Rok vydání: 2022
Předmět:
Zdroj: The Journal of Immunology. 208:110.17-110.17
ISSN: 1550-6606
0022-1767
Popis: Naive T cell activation in secondary lymphoid organs such as lymph nodes (LNs) occurs upon recognition of cognate antigens presented by antigen presenting cells (APCs). T cell activation requires cytoskeleton rearrangement and sustained interactions with APCs. Ena/VASP proteins are a family of cytoskeletal effector proteins responsible for actin polymerization and are frequently found at the leading edge of motile cells. Ena/VASP proteins have been implicated in motility and adhesion in various cell types, but their role in primary T cell activation has not been explored. Our goal was to determine the contribution of Ena/VASP proteins to T cell activation and expansion in vivo. Our results showed that naïve T cells from Ena/VASP-deficient mice have a significant reduction in antigen-specific T cell accumulation following Listeria monocytogenes infection. The kinetics of antigen-specific T cell impairment were further confirmed in Ena/VASP-deficient T cells stimulated via dendritic cell immunization. To investigate the cause of this T cell expansion defect, we analyzed T cell-APC interactions in vivo by 2-photon microscopy and observed fewer Ena/VASP-deficient naïve T cells interacting with APCs in LNs during priming. We also found that Ena/VASP-deficient T cells formed conjugates with significantly less actin polymerization at the T cell-APC synapse, and that these conjugates were less stable than their WT counterparts. Thus, we conclude that Ena/VASP proteins contribute to T cell actin remodeling downstream of T-APC interactions required for the initiation of stable T cell conjugates during APC scanning and for efficient activation and expansion of T cells in vivo. Supported by NIH (R01AI125553; T32AI007405)
Databáze: OpenAIRE
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