T cells' immunological synapses induce polarization of brain astrocytes in vivo and in vitro: a novel astrocyte response mechanism to cellular injury

• Published in: PloS one 2008-08, Vol.3 (8), p.e2977-e2977
• Main Authors: Barcia, Carlos, Sanderson, Nicholas S R, Barrett, Robert J, Wawrowsky, Kolja, Kroeger, Kurt M, Puntel, Mariana, Liu, Chunyan, Castro, Maria G, Lowenstein, Pedro R
• Format: Article
• Language: English
• Subjects: Adenoviridae; Animals; Antiviral agents; Apoptosis; Astrocytes; Astrocytes - cytology; Astrocytes - immunology; Astrocytes - physiology; Brain; Brain - physiology; Brain research; Cancer; Cell Biology/Neuronal and Glial Cell Biology; Cell Polarity - physiology; Cell signaling; Coculture Techniques; Corpus Striatum - drug effects; Corpus Striatum - physiology; Corpus Striatum - virology; Cytoskeleton; Effector cells; Fibroblasts; Gene therapy; Genetics and Genomics/Gene Therapy; Golgi apparatus; Governors; Health aspects; HIV; Human immunodeficiency virus; Hypertrophy; Immune clearance; Immune response; Immunological synapses; Immunology; Immunology/Cellular Microbiology and Pathogenesis; Immunology/Immune Response; Immunology/Immunity to Infections; Infectious Diseases/HIV Infection and AIDS; Infectious Diseases/Viral Infections; Intercellular signalling; Lymphocytes; Lymphocytes T; Male; Medicine; Microscopy, Confocal; Morphology; Neurodegeneration; Neurological Disorders/Infectious Diseases of the Nervous System; Neuroscience/Neuronal and Glial Cell Biology; Pharmacology; Physicians; Polarity; Polarization; Rats; Rats, Sprague-Dawley; Shear stress; Shear stresses; Spleen - cytology; Spleen - immunology; Spleen - physiology; Spleen - virology; Stacks; Stroke; Synapses; Synapses - physiology; Synaptogenesis; T cells; T-Lymphocytes - immunology; Thymidine Kinase - administration & dosage; Thymidine Kinase - pharmacology; Trauma; Traumatic brain injury; Virology/Host Antiviral Responses
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0002977

Astrocytes usually respond to trauma, stroke, or neurodegeneration by undergoing cellular hypertrophy, yet, their response to a specific immune attack by T cells is poorly understood. Effector T cells establish specific contacts with target cells, known as immunological synapses, during clearance of virally infected cells from the brain. Immunological synapses mediate intercellular communication between T cells and target cells, both in vitro and in vivo. How target virally infected astrocytes respond to the formation of immunological synapses established by effector T cells is unknown. Herein we demonstrate that, as a consequence of T cell attack, infected astrocytes undergo dramatic morphological changes. From normally multipolar cells, they become unipolar, extending a major protrusion towards the immunological synapse formed by the effector T cells, and withdrawing most of their finer processes. Thus, target astrocytes become polarized towards the contacting T cells. The MTOC, the organizer of cell polarity, is localized to the base of the protrusion, and Golgi stacks are distributed throughout the protrusion, reaching distally towards the immunological synapse. Thus, rather than causing astrocyte hypertrophy, antiviral T cells cause a major structural reorganization of target virally infected astrocytes. Astrocyte polarization, as opposed to hypertrophy, in response to T cell attack may be due to T cells providing a very focused attack, and thus, astrocytes responding in a polarized manner. A similar polarization of Golgi stacks towards contacting T cells was also detected using an in vitro allogeneic model. Thus, different T cells are able to induce polarization of target astrocytes. Polarization of target astrocytes in response to immunological synapses may play an important role in regulating the outcome of the response of astrocytes to attacking effector T cells, whether during antiviral (e.g. infected during HIV, HTLV-1, HSV-1 or LCMV infection), anti-transplant, autoimmune, or anti-tumor immune responses in vivo and in vitro.