title: Recovery from EAE is associated with decreased survival of encephalitogenic T cells in the CNS of B7-1/B7-2-deficient mice.
abstract: Adoptive transfer experiments using C57BL/6 mice lacking B7-1 and B7-2 as recipients of wt (wt) encephalitogenic T cells demonstrate a key role for B7 costimulation during the effector phase of experimental autoimmune encephalomyelitis (EAE). Following transfer of encephalitogenic T cells, B7-1/B7-2-deficient (-/-) recipients develop a transient and mild disease as compared to wt recipients. To understand the mechanism by which B7-1/B7-2 may influence the effector phase of EAE, we analyzed T cells, pro-inflammatory cytokines and chemokines within the CNS of wt and B7-1/B7-2-/- recipients at different times after adoptive transfer of activated myelin specific T cells. There was a marked decline in T cells and inflammatory mediators in the CNS of B7-1/B7-2-/- recipients by day 30 post transfer. B7-1/B7-2-/- mice developed more TUNEL+ apoptotic cells in the parenchyma and greater ratios of TUNEL+ cells/parenchymal foci than wt mice resulting in virtual disappearance of parenchymal foci. Therefore, without B7-1 and B7-2 costimulation in the target organ, there is increased T cell apoptosis and attenuation of inflammation. These results indicate that B7-1 and B7-2 provide critical costimulatory signals for sustaining survival of pathogenic T cells within the central nervous system parenchyma during the effector phase of EAE and suggest novel treatment approaches in the effector phase of autoimmune diseases.
authors.affiliation: Immunology Research Division, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, 221 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Tammy T
authors.initials: TT
authors.lastname: Chang
authors.forename: Raymond A
authors.initials: RA
authors.lastname: Sobel
authors.forename: Tao
authors.initials: T
authors.lastname: Wei
authors.forename: Richard M
authors.initials: RM
authors.lastname: Ransohoff
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Kuchroo
authors.forename: Arlene H
authors.initials: AH
authors.lastname: Sharpe
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics*; D017209:Apoptosis / Q000502:physiology; D018122:B7-1 Antigen / Q000235:genetics*; D051940:B7-2 Antigen; D002470:Cell Survival / Q000502:physiology; D002490:Central Nervous System / Q000378:metabolism / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics*; D051379:Mice; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D008562:Membrane Glycoproteins