T Cells’ Immunological Synapses Induce Polarization of Brain Astrocytes In Vivo and In Vitro: A Novel Astrocyte Response Mechanism to Cellular Injury

BARCIA; SANDERSON; BARRET; WAWROSKY; KROEGER; PUNTEL; LIU; CASTRO; LOWENSTEIN

PLOS ONE

www.plosone.org

Año: 2008

1932-6203

Background: 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 withtarget cells, known as immunological synapses, during clearance of virally infected cells from the brain. Immunologicalsynapses mediate intercellular communication between T cells and target cells, both in vitro and in vivo. How target virallyinfected astrocytes respond to the formation of immunological synapses established by effector T cells is unknown.Findings: Herein we demonstrate that, as a consequence of T cell attack, infected astrocytes undergo dramaticmorphological changes. From normally multipolar cells, they become unipolar, extending a major protrusion towards theimmunological synapse formed by the effector T cells, and withdrawing most of their finer processes. Thus, target astrocytesbecome polarized towards the contacting T cells. The MTOC, the organizer of cell polarity, is localized to the base of theprotrusion, and Golgi stacks are distributed throughout the protrusion, reaching distally towards the immunologicalsynapse. Thus, rather than causing astrocyte hypertrophy, antiviral T cells cause a major structural reorganization of targetvirally infected astrocytes.Conclusions: Astrocyte polarization, as opposed to hypertrophy, in response to T cell attack may be due to T cells providing avery focused attack, and thus, astrocytes responding in a polarized manner. A similar polarization of Golgi stacks towardscontacting T cells was also detected using an in vitro allogeneic model. Thus, different T cells are able to induce polarization oftarget astrocytes. Polarization of target astrocytes in response to immunological synapses may play an important role inregulating the outcome of the response of astrocytes to attacking effector T cells, whether during antiviral (e.g. infected duringHIV, HTLV-1, HSV-1 or LCMV infection), anti-transplant, autoimmune, or anti-tumor immune responses in vivo and in vitro.