Intestinal intraepithelial lymphocytes exert potent protective cytotoxic activity during an acute virus infection.
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.
Müller
S
S
Institute of Pathology, Division of Immunopathology, University of Bern, Bern, Switzerland.
Bühler-Jungo
M
M
Mueller
C
C
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
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