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  • 1
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    HIV-infected T cells are migratory vehicles for viral dissemination (2012)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2012-08-03
    Description: After host entry through mucosal surfaces, human immunodeficiency virus-1 (HIV-1) disseminates to lymphoid tissues to establish a generalized infection of the immune system. The mechanisms by which this virus spreads among permissive target cells locally during the early stages of transmission and systemically during subsequent dissemination are not known. In vitro studies suggest that the formation of virological synapses during stable contacts between infected and uninfected T cells greatly increases the efficiency of viral transfer. It is unclear, however, whether T-cell contacts are sufficiently stable in vivo to allow for functional synapse formation under the conditions of perpetual cell motility in epithelial and lymphoid tissues. Here, using multiphoton intravital microscopy, we examine the dynamic behaviour of HIV-infected T cells in the lymph nodes of humanized mice. We find that most productively infected T cells migrate robustly, resulting in their even distribution throughout the lymph node cortex. A subset of infected cells formed multinucleated syncytia through HIV envelope-dependent cell fusion. Both uncoordinated motility of syncytia and adhesion to CD4(+) lymph node cells led to the formation of long membrane tethers, increasing cell lengths to up to ten times that of migrating uninfected T cells. Blocking the egress of migratory T cells from the lymph nodes into efferent lymph vessels, and thus interrupting T-cell recirculation, limited HIV dissemination and strongly reduced plasma viraemia. Thus, we have found that HIV-infected T cells are motile, form syncytia and establish tethering interactions that may facilitate cell-to-cell transmission through virological synapses. Migration of T cells in lymph nodes therefore spreads infection locally, whereas their recirculation through tissues is important for efficient systemic viral spread, suggesting new molecular targets to antagonize HIV infection.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3470742/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3470742/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Murooka, Thomas T -- Deruaz, Maud -- Marangoni, Francesco -- Vrbanac, Vladimir D -- Seung, Edward -- von Andrian, Ulrich H -- Tager, Andrew M -- Luster, Andrew D -- Mempel, Thorsten R -- P01 AI0178897/AI/NIAID NIH HHS/ -- P30 AI060354/AI/NIAID NIH HHS/ -- P30 AR042689/AR/NIAMS NIH HHS/ -- P30 DK043351/DK/NIDDK NIH HHS/ -- P30AI060354/AI/NIAID NIH HHS/ -- R01 CA150975/CA/NCI NIH HHS/ -- R56 AI097052/AI/NIAID NIH HHS/ -- T32 AI007387/AI/NIAID NIH HHS/ -- England -- Nature. 2012 Oct 11;490(7419):283-7. doi: 10.1038/nature11398. Epub 2012 Aug 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22854780" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; CD4-Positive T-Lymphocytes/*virology ; Cell Movement ; Cells, Cultured ; Disease Models, Animal ; Female ; Giant Cells ; HIV/*immunology ; HIV Infections/*immunology/transmission/*virology ; Humans ; Lymph Nodes/virology ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Mice, Transgenic
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 2
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    VACCINES. A mucosal vaccine against Chlamydia trachomatis generates two waves of protective memory T cells (2015)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2015-06-20
    Description: Genital Chlamydia trachomatis (Ct) infection induces protective immunity that depends on interferon-gamma-producing CD4 T cells. By contrast, we report that mucosal exposure to ultraviolet light (UV)-inactivated Ct (UV-Ct) generated regulatory T cells that exacerbated subsequent Ct infection. We show that mucosal immunization with UV-Ct complexed with charge-switching synthetic adjuvant particles (cSAPs) elicited long-lived protection in conventional and humanized mice. UV-Ct-cSAP targeted immunogenic uterine CD11b(+)CD103(-) dendritic cells (DCs), whereas UV-Ct accumulated in tolerogenic CD11b(-)CD103(+) DCs. Regardless of vaccination route, UV-Ct-cSAP induced systemic memory T cells, but only mucosal vaccination induced effector T cells that rapidly seeded uterine mucosa with resident memory T cells (T(RM) cells). Optimal Ct clearance required both T(RM) seeding and subsequent infection-induced recruitment of circulating memory T cells. Thus, UV-Ct-cSAP vaccination generated two synergistic memory T cell subsets with distinct migratory properties.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4605428/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4605428/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stary, Georg -- Olive, Andrew -- Radovic-Moreno, Aleksandar F -- Gondek, David -- Alvarez, David -- Basto, Pamela A -- Perro, Mario -- Vrbanac, Vladimir D -- Tager, Andrew M -- Shi, Jinjun -- Yethon, Jeremy A -- Farokhzad, Omid C -- Langer, Robert -- Starnbach, Michael N -- von Andrian, Ulrich H -- 1 R01-EB015419-01/EB/NIBIB NIH HHS/ -- AI069259/AI/NIAID NIH HHS/ -- AI078897/AI/NIAID NIH HHS/ -- AI095261/AI/NIAID NIH HHS/ -- AI111595/AI/NIAID NIH HHS/ -- P01 AI078897/AI/NIAID NIH HHS/ -- P30-AI060354/AI/NIAID NIH HHS/ -- R00 CA160350/CA/NCI NIH HHS/ -- R01 AI039558/AI/NIAID NIH HHS/ -- R01 AI062827/AI/NIAID NIH HHS/ -- R01 AI069259/AI/NIAID NIH HHS/ -- R01 AI072252/AI/NIAID NIH HHS/ -- R01 AI111595/AI/NIAID NIH HHS/ -- R01 AI39558/AI/NIAID NIH HHS/ -- R37-EB000244/EB/NIBIB NIH HHS/ -- T32 HL066987/HL/NHLBI NIH HHS/ -- U19 AI095261/AI/NIAID NIH HHS/ -- U19 AI113187/AI/NIAID NIH HHS/ -- U54-CA119349/CA/NCI NIH HHS/ -- U54-CA151884/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2015 Jun 19;348(6241):aaa8205. doi: 10.1126/science.aaa8205.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA. uva@hms.harvard.edu georg_stary@hms.harvard.edu. ; Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA. ; Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA 02139, USA. Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. ; Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. ; Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. ; Sanofi Pasteur, Cambridge, MA 02139, USA. ; Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. King Abdulaziz University, Jeddah, Saudi Arabia. ; Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA. Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA. uva@hms.harvard.edu georg_stary@hms.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26089520" target="_blank"〉PubMed〈/a〉
    Keywords: Adjuvants, Immunologic/administration & dosage ; Animals ; Antigens, CD/immunology ; Antigens, CD11/immunology ; Bacterial Vaccines/administration & dosage/*immunology ; CD8-Positive T-Lymphocytes/immunology ; Chlamydia Infections/*prevention & control ; Chlamydia trachomatis/*immunology/radiation effects ; Dendritic Cells/immunology ; Female ; *Immunologic Memory ; Integrin alpha Chains/immunology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mucous Membrane/immunology ; Nanoparticles/administration & dosage ; T-Lymphocyte Subsets/immunology ; Th1 Cells/*immunology ; Ultraviolet Rays ; Uterus/*immunology ; Vaccination/methods ; Vaccines, Inactivated/administration & dosage/immunology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 3
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    Chemokine receptor CXCR3 and its ligands CXCL9 and CXCL10 are required for the development of murine cerebral malaria (2008)
    National Academy of Sciences
    Details
    Publication Date: 2008-03-17
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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