NDLI: Regulatory T cells in central nervous system injury: a double-edged sword.

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Regulatory T cells in central nervous system injury: a double-edged sword.

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Regulatory T cells in central nervous system injury: a double-edged sword.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Zheng, Jingjing Lorenz, Ulrike Kipnis, Jonathan Smirnov, Igor Walsh, James T. Tung, Kenneth
Description	Author Affiliation: Walsh JT ( Center for Brain Immunology and Glia, School of Medicine, University of Virginia, Charlottesville, VA 22908); Zheng J ( Center for Brain Immunology and Glia, School of Medicine, University of Virginia, Charlottesville, VA 22908); Smirnov I ( Center for Brain Immunology and Glia, School of Medicine, University of Virginia, Charlottesville, VA 22908); Lorenz U ( Beirne Carter Center for Immunology Research, University of Virginia, Charlottesville, VA 22908); Tung K ( Department of Microbiology, Immunology, and Cancer Biology, School of Medicine, University of Virginia, Charlottesville, VA 22908); Kipnis J ( Center for Brain Immunology and Glia, School of Medicine, University of Virginia, Charlottesville, VA 22908)
Abstract	Previous research investigating the roles of T effector (T(eff)) and T regulatory (T(reg)) cells after injury to the CNS has yielded contradictory conclusions, with both protective and destructive functions being ascribed to each of these T cell subpopulations. In this work, we study this dichotomy by examining how regulation of the immune system affects the response to CNS trauma. We show that, in response to CNS injury, T(eff) and T(reg) subsets in the CNS-draining deep cervical lymph nodes are activated, and surgical resection of these lymph nodes results in impaired neuronal survival. Depletion of T(reg), not surprisingly, induces a robust T(eff) response in the draining lymph nodes and is associated with impaired neuronal survival. Interestingly, however, injection of exogenous T(reg) cells, which limits the spontaneous beneficial immune response after CNS injury, also impairs neuronal survival. We found that no T(reg) accumulate at the site of CNS injury, and that changes in T(reg) numbers do not alter the amount of infiltration by other immune cells into the site of injury. The phenotype of macrophages at the site, however, is affected: both addition and removal of T(reg) negatively impact the numbers of macrophages with alternatively activated (tissue-building) phenotype. Our data demonstrate that neuronal survival after CNS injury is impaired when T(reg) cells are either removed or added. With this exacerbation of neurodegeneration seen with both addition and depletion of T(reg), we recommend exercising extreme caution when considering the therapeutic targeting of T(reg) cells after CNS injury, and possibly in chronic neurodegenerative conditions.
ISSN	00221767
e-ISSN	15506606
DOI	10.4049/jimmunol.1302401
Journal	The Journal of Immunology
Issue Number	10
Volume Number	193
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2014-11-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Neurons Immunology Optic Nerve Injuries Retina T-lymphocytes, Regulatory Animals Cd8-positive T-lymphocytes Pathology Cell Survival Immunophenotyping Lymph Nodes Lymphocyte Activation Macrophages Mice Mice, Inbred C57bl Injuries Transplantation Research Support, N.i.h., Extramural Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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