title: Spatiotemporally Distinct Interactions with Dendritic Cell Subsets Facilitates CD4+ and CD8+ T Cell Activation to Localized Viral Infection.
abstract: The dynamics of when and where CD4(+) T cells provide help for CD8(+) T cell priming and which dendritic cells (DCs) activate CD4(+) T cells in vivo after localized infection are poorly understood. By using a cutaneous herpes simplex virus infection model combined with intravital 2-photon imaging of the draining lymph node (LN) to concurrently visualize pathogen-specific CD4(+) and CD8(+) T cells, we found that early priming of CD4(+) T cells involved clustering with migratory skin DCs. CD8(+) T cells did not interact with migratory DCs and their activation was delayed, requiring later clustering interactions with LN-resident XCR1(+) DCs. CD4(+) T cells interacted with these late CD8(+) T cell clusters on resident XCR1(+) DCs. Together, these data reveal asynchronous T cell activation by distinct DC subsets and highlight the key role of XCR1(+) DCs as the central platform for cytotoxic T lymphocyte activation and the delivery of CD4(+) T cell help.
authors: Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Parkville, VIC 3010, Australia; The Australian Research Council Centre of Excellence in Advanced Molecular Imaging, The University of Melbourne, Parkville, VIC 3010, Australia.
authors: Jyh Liang
authors: JL
authors: Hor
authors: Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Parkville, VIC 3010, Australia.
authors: Paul G
authors: PG
authors: Whitney
authors: Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Parkville, VIC 3010, Australia; The Australian Research Council Centre of Excellence in Advanced Molecular Imaging, The University of Melbourne, Parkville, VIC 3010, Australia.
authors: Ali
authors: A
authors: Zaid
authors: Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Parkville, VIC 3010, Australia.
authors: Andrew G
authors: AG
authors: Brooks
authors: Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Parkville, VIC 3010, Australia; The Australian Research Council Centre of Excellence in Advanced Molecular Imaging, The University of Melbourne, Parkville, VIC 3010, Australia.
authors: William R
authors: WR
authors: Heath
authors: Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Parkville, VIC 3010, Australia; The Australian Research Council Centre of Excellence in Advanced Molecular Imaging, The University of Melbourne, Parkville, VIC 3010, Australia. Electronic address: smue@unimelb.edu.au.
authors: Scott N
authors: SN
authors: Mueller
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D005456:Fluorescent Dyes / Q000737:chemistry; D006561:Herpes Simplex / Q000276:immunology / Q000378:metabolism / Q000821:virology; D054884:Host-Pathogen Interactions / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology* / Q000821:virology; D008213:Lymphocyte Activation / Q000276:immunology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D036641:Microscopy, Fluorescence, Multiphoton; D019707:Receptors, Chemokine / Q000276:immunology / Q000378:metabolism; D012235:Rhodamines / Q000737:chemistry; D018139:Simplexvirus / Q000276:immunology / Q000502:physiology
chemical_list: D005456:Fluorescent Dyes; D019707:Receptors, Chemokine; D012235:Rhodamines; C551408:XC chemokine receptor 1, mouse; C009434:tetramethylrhodamine isothiocyanate