title: Intestinal intraepithelial lymphocytes exert potent protective cytotoxic activity during an acute virus infection.
abstract: After systemic infection of mice with 104 PFU of lymphocytic choriomeningitis virus (LCMV), infected cells are detected simultaneously in various organs, including spleen and intestinal mucosa. Most notably, virus-infected cells are also present among CD11c+ dendritic cells in the subepithelial area of the small intestinal mucosa. Some of these virus-infected cells are in close spatial association with intestinal intraepithelial lymphocytes (IEL). Therefore, we compared virus-specific cytotoxic activity of CD8 splenocytes with that of IEL subsets. While ex vivo isolated TCRalphabeta+CD8alphaalpha+ IEL exert only minimal virus-specific cytotoxicity, maximum specific killing mediated by TCRalphabeta+CD8alphabeta+ IEL on day 8 postinfection exceeds maximum cytotoxic activity observed with CD8 splenocytes when assessed in vitro. Maximum cytotoxic activity of IEL is preceded by peak perforin and granzyme B mRNA expression in IEL around day 6 postinfection, suggesting a recent activation in situ. The antivirus cytotoxicity of in vivo primed IEL is further demonstrated by the protection from virus production in the spleen of mice infected with LCMV 10 h before adoptive cell transfer. These data indicate a potent priming of LCMV-specific IEL in situ after systemic LCMV infection and suggest that cytotoxic IEL markedly contribute to the elimination of virus-infected cells in the intestinal mucosa.
authors.affiliation: Institute of Pathology, Division of Immunopathology, University of Bern, Bern, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Müller
authors.forename: M
authors.initials: M
authors.lastname: Bühler-Jungo
authors.forename: C
authors.initials: C
authors.lastname: Mueller
mesh_terms: D000208:Acute Disease; D000818:Animals; D016827:CD8 Antigens / Q000096:biosynthesis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology; D053804:Granzymes; D007413:Intestinal Mucosa / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D007700:Kinetics; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D008216:Lymphocytic Choriomeningitis / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D008264:Macrophages / Q000276:immunology / Q000821:virology; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger / Q000096:biosynthesis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis; D012697:Serine Endopeptidases / Q000235:genetics; D013154:Spleen / Q000276:immunology / Q000473:pathology / Q000821:virology; D015854:Up-Regulation / Q000276:immunology; D014779:Virus Replication / Q000276:immunology
chemical_list: D016827:CD8 Antigens; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; D054353:Perforin; D053804:Granzymes; C509214:Gzmb protein, mouse; D012697:Serine Endopeptidases