title: Simian immunodeficiency virus (SIV)-specific CTL are present in large numbers in livers of SIV-infected rhesus monkeys.
abstract: The immunopathogenesis of AIDS-associated hepatitis was explored in the SIV/rhesus monkey model. The livers of SIV-infected monkeys showed a mild hepatitis, with a predominantly CD8+ T lymphocyte infiltration in the periportal fields and sinusoids. These liver-associated CD8+ T cells were comprised of a high percentage of SIV-specific CTL as defined by MHC class I/Gag peptide tetramer binding and Gag peptide epitope-specific lytic activity. There was insufficient viral replication in these livers to account for attracting this large number of functional virus-specific CTL to the liver. There was also no evidence that the predominant population of CTL were functionally end-stage cells trapped in the liver and destined to undergo apoptotic cell death in that organ. Interestingly, we noted that liver tetramer-binding cells showed an increased expression of CD62L, an adhesion molecule usually only rarely expressed on tetramer-binding cells. This observation suggests that the expression of specific adhesion molecules by CTL might facilitate the capture of these cells in the liver. These results demonstrate that functional SIV-specific CD8+ T cells are present in large numbers in the liver of chronically SIV-infected monkeys. Thus, the liver may be a trap for virus-specific cytotoxic T cells.
authors.affiliation: Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. jschmitz@caregroup.harvard.edu
authors.forename: J E
authors.initials: JE
authors.lastname: Schmitz
authors.forename: M J
authors.initials: MJ
authors.lastname: Kuroda
authors.forename: R S
authors.initials: RS
authors.lastname: Veazey
authors.forename: A
authors.initials: A
authors.lastname: Seth
authors.forename: W M
authors.initials: WM
authors.lastname: Taylor
authors.forename: C E
authors.initials: CE
authors.lastname: Nickerson
authors.forename: M A
authors.initials: MA
authors.lastname: Lifton
authors.forename: P J
authors.initials: PJ
authors.lastname: Dailey
authors.forename: M A
authors.initials: MA
authors.lastname: Forman
authors.forename: P
authors.initials: P
authors.lastname: Racz
authors.forename: K
authors.initials: K
authors.lastname: Tenner-Racz
authors.forename: N L
authors.initials: NL
authors.lastname: Letvin
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000032:analysis* / Q000235:genetics; D015683:Gene Products, gag / Q000276:immunology; D006520:Hepatitis, Animal / Q000276:immunology / Q000473:pathology; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D016130:Immunophenotyping; D019041:L-Selectin / Q000096:biosynthesis / Q000097:blood; D008099:Liver / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D018655:Lymphocyte Count; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000473:pathology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism / Q000473:pathology* / Q000821:virology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D015683:Gene Products, gag; D015395:Histocompatibility Antigens Class I; C110764:Mamu-A 01 antigen; D019041:L-Selectin