PMID- 24651727 OWN - NLM STAT- MEDLINE DCOM- 20151020 LR - 20220317 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 4 DP - 2014 Mar 21 TI - Immune privilege of the CNS is not the consequence of limited antigen sampling. PG - 4422 LID - 10.1038/srep04422 [doi] LID - 4422 AB - 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. FAU - Harris, Melissa G AU - Harris MG AD - 1] Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI [2] Neuroscience Training Program, University of Wisconsin-Madison, Madison, WI. FAU - Hulseberg, Paul AU - Hulseberg P AD - 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. FAU - Ling, Changying AU - Ling C AD - 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. FAU - Karman, Jozsef AU - Karman J AD - 1] Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI [2] Genzyme Corporation, Cambridge, MA. FAU - Clarkson, Benjamin D AU - Clarkson BD AD - 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. FAU - Harding, Jeffrey S AU - Harding JS AD - 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. FAU - Zhang, Mengxue AU - Zhang M AD - Department of Pathology, Peking University, Beijing, China. FAU - Sandor, Adam AU - Sandor A AD - Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI. FAU - Christensen, Kelsey AU - Christensen K AD - Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI. FAU - Nagy, Andras AU - Nagy A AD - Mount Sinai Hospital, Toronto, Ontario. FAU - Sandor, Matyas AU - Sandor M AD - Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI. FAU - Fabry, Zsuzsanna AU - Fabry Z AD - Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI. LA - eng GR - T32 GM081061/GM/NIGMS NIH HHS/United States GR - R01-AI048087/AI/NIAID NIH HHS/United States GR - R01-NS37570/NS/NINDS NIH HHS/United States GR - T32 GM007507/GM/NIGMS NIH HHS/United States GR - R01 AI048087/AI/NIAID NIH HHS/United States GR - R01 NS037570/NS/NINDS NIH HHS/United States GR - T32-GM007507/GM/NIGMS NIH HHS/United States GR - R01 NS076946/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20140321 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Antigens) RN - 0 (Recombinant Fusion Proteins) RN - 0 (enhanced green fluorescent protein) RN - 147336-22-9 (Green Fluorescent Proteins) RN - 9006-59-1 (Ovalbumin) SB - IM MH - Adaptive Immunity MH - Animals MH - Antigens/chemistry/*immunology MH - CD4-Positive T-Lymphocytes/cytology/immunology MH - CD8-Positive T-Lymphocytes/cytology/immunology MH - Central Nervous System/*immunology/metabolism MH - Epithelial Cells/cytology/*immunology MH - Female MH - Gene Expression MH - Green Fluorescent Proteins/genetics/immunology MH - *Immunity, Innate MH - Intestinal Mucosa/cytology/*immunology MH - Lymphocyte Activation MH - Male MH - Mice MH - Mice, Transgenic MH - Oligodendroglia/cytology/*immunology MH - Ovalbumin/genetics/immunology MH - Recombinant Fusion Proteins/genetics/immunology PMC - PMC3961746 EDAT- 2014/03/22 06:00 MHDA- 2015/10/21 06:00 PMCR- 2014/03/21 CRDT- 2014/03/22 06:00 PHST- 2014/01/09 00:00 [received] PHST- 2014/02/21 00:00 [accepted] PHST- 2014/03/22 06:00 [entrez] PHST- 2014/03/22 06:00 [pubmed] PHST- 2015/10/21 06:00 [medline] PHST- 2014/03/21 00:00 [pmc-release] AID - srep04422 [pii] AID - 10.1038/srep04422 [doi] PST - epublish SO - Sci Rep. 2014 Mar 21;4:4422. doi: 10.1038/srep04422.