Effector and suppressor roles for LFA-1 during the development of experimental autoimmune encephalomyelitis |
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| Authors: | Kari J Dugger Kurt R Zinn Casey Weaver Daniel C Bullard Scott R Barnum |
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| Institution: | 1. Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, United States;2. Department of Radiology, University of Alabama at Birmingham, Birmingham, AL 35294, United States;3. Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, United States;4. Department of Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, United States;5. Department of Neurology, University of Alabama at Birmingham, Birmingham, AL 35294, United States;1. Albany College of Pharmacy & Health Sciences, Colchester, Vermont;2. University of Vermont Medical Center, Burlington, Vermont;1. Merck Research Laboratories, 901 California Avenue, Palo Alto, CA 94304, USA;2. Molecular Immunology and Inflammation Branch, National Institute of Arthritis, & Musculoskeletal and Skin Diseases, National Institute of Health, Bethesda, MD 20892, USA;1. Department of Neurology, Yale School of Medicine, New Haven, CT, United States;2. Department of Immunobiology, Yale School of Medicine, New Haven, CT, United States;3. Broad Institute of MIT and Harvard, Cambridge, MA, United States;1. Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, Taibai North Road 229, Xi''an, Shaanxi, 710069, China;2. Shaanxi R&D Center of Biomaterials and Fermentation Engineering, School of Chemical Engineering, Northwest University, Taibai North Road 229, Xi''an, Shaanxi, 710069, China;3. Biotech & Biomed Research Institute, Northwest University, Taibai North Road 229, Xi''an, Shaanxi, 710069, China;4. Nutrition and Food Safety Engineering Research Center of Shaanxi Province, College of Public Health, School of Medicine, Xi''an Jiaotong University, Xi''an, 710061, China |
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| Abstract: | LFA-1 (CD11a/CD18) is a member of the β2-integrin family of adhesion molecules important in leukocyte trafficking and activation. Although LFA-1 is thought to contribute to the development of experimental autoimmune encephalomyelitis (EAE) primarily through its functions on effector T cells, its importance on other leukocyte populations remains unexplored. To address this question, we performed both adoptive transfer EAE experiments involving CD11a?/? mice and trafficking studies using bioluminescent T cells expressing luciferase under the control of a CD2 promoter (T-lux cells). Transfer of encephalitogenic CD11a?/? T cells to wild type mice resulted in a significant reduction in overall EAE severity compared to control transfers. We also observed, using in vivo imaging techniques, that CD11a?/? T-lux cells readily infiltrated lymph nodes and the CNS of wild type recipients with kinetics comparable to CD11a+/+ transfers, although their overall numbers in these organs were reduced. Surprisingly, transfer of encephalitogenic wild type T cells to CD11a?/? mice induced a severe and sometimes fatal EAE disease course, associated with massive T cell infiltration and proliferation in the CNS. These data indicate that LFA-1 expression on leukocytes in recipient mice plays an important immunomodulatory role in EAE. Thus, LFA-1 acts as a key regulatory adhesion molecule during the development of EAE, serving both pro- and anti-inflammatory roles in disease pathogenesis. |
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