title: Immune privilege of the CNS is not the consequence of limited antigen sampling.
abstract: Central nervous system (CNS) immune privilege is complex, and it is still not understood how CNS antigens are sampled by the peripheral immune system under steady state conditions. To compare antigen sampling from immune-privileged or nonprivileged tissues, we created transgenic mice with oligodendrocyte or gut epithelial cell expression of an EGFP-tagged fusion protein containing ovalbumin (OVA) antigenic peptides and tested peripheral anti-OVA peptide-specific sentinel OT-I and OT-II T cell activation. We report that oligodendrocyte or gut antigens are sampled similarly, as determined by comparable levels of OT-I T cell activation. However, activated T cells do not access the CNS under steady state conditions. These data show that afferent immunity is normally intact as there is no barrier at the antigen sampling level, but that efferent immunity is restricted. To understand how this one-sided surveillance contributes to CNS immune privilege will help us define mechanisms of CNS autoimmune disease initiation.
authors.affiliation: 1] Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI [2] Neuroscience Training Program, University of Wisconsin-Madison, Madison, WI.
authors.forename: Melissa G
authors.initials: MG
authors.lastname: Harris
authors.affiliation: 1] Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI [2] Cellular and Molecular Pathology Graduate Program, University of Wisconsin-Madison, Madison, WI.
authors.forename: Paul
authors.initials: P
authors.lastname: Hulseberg
authors.affiliation: 1] Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI [2] Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI.
authors.forename: Changying
authors.initials: C
authors.lastname: Ling
authors.affiliation: 1] Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI [2] Genzyme Corporation, Cambridge, MA.
authors.forename: Jozsef
authors.initials: J
authors.lastname: Karman
authors.affiliation: 1] Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI [2] Cellular and Molecular Pathology Graduate Program, University of Wisconsin-Madison, Madison, WI.
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Clarkson
authors.affiliation: 1] Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI [2] Cellular and Molecular Pathology Graduate Program, University of Wisconsin-Madison, Madison, WI.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Harding
authors.affiliation: Department of Pathology, Peking University, Beijing, China.
authors.forename: Mengxue
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI.
authors.forename: Adam
authors.initials: A
authors.lastname: Sandor
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI.
authors.forename: Kelsey
authors.initials: K
authors.lastname: Christensen
authors.affiliation: Mount Sinai Hospital, Toronto, Ontario.
authors.forename: Andras
authors.initials: A
authors.lastname: Nagy
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI.
authors.forename: Matyas
authors.initials: M
authors.lastname: Sandor
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Fabry
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D000941:Antigens / Q000737:chemistry / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002490:Central Nervous System / Q000276:immunology* / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology*; D005260:Female; D015870:Gene Expression; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000276:immunology; D007113:Immunity, Innate; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009836:Oligodendroglia / Q000166:cytology / Q000276:immunology*; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology
chemical_list: D000941:Antigens; D011993:Recombinant Fusion Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D010047:Ovalbumin