title: Hepatic CD1d expression in hepatitis C virus infection and recognition by resident proinflammatory CD1d-reactive T cells.
abstract: A subset of CD161(+)CD56(+/-) NKT cells can recognize glycolipids presented by CD1d and positively or negatively regulate inflammatory responses, including those implicated in several models of hepatitis. CD1d is expressed at very low levels in the healthy liver, but there is a large fraction of CD161(+)CD56(+) NKT cells. There are high levels of nonclassical proinflammatory hepatic CD1d-reactive T cells in hepatitis C virus (HCV) infection. Hepatic inflammatory cells and biliary cells adjacent to portal tract fibrotic areas of HCV-infected donors specifically up-regulated CD1d. A hepatocyte cell line expressing minimal CD1d was efficiently recognized by hepatic CD1d-reactive T cells, suggesting a role for these cells in disease. Hepatic CD1d-reactive T cells from HCV-positive as well as negative donors produced large amounts of IFN-gamma with some IL-13, but only rarely detectable IL-4. We confirmed large numbers of hepatic CD161(+) T cells, lower levels of CD56(+) T cells, and small numbers of classic invariant NKT cells. However, hepatic CD1d-reactivity was not restricted to any of these populations. We suggest virally infected hepatic cells can process potent CD1d-presented liver Ag(s), for surveillance by resident Th1 hepatic CD1d-reactive T cells. This process may be beneficial in acute viral clearance, but in chronic infection could contribute to liver injury.
authors.affiliation: Infectious Diseases Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Durante-Mangoni
authors.forename: RuoJie
authors.initials: R
authors.lastname: Wang
authors.forename: Angela
authors.initials: A
authors.lastname: Shaulov
authors.forename: Qi
authors.initials: Q
authors.lastname: He
authors.forename: Imad
authors.initials: I
authors.lastname: Nasser
authors.forename: Nezam
authors.initials: N
authors.lastname: Afdhal
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: Koziel
authors.forename: Mark A
authors.initials: MA
authors.lastname: Exley
mesh_terms: D000208:Acute Disease; D017951:Antigen Presentation; D018949:Antigens, CD1 / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D055610:Antigens, CD1d; D000954:Antigens, Surface / Q000032:analysis; D019002:CD56 Antigen / Q000032:analysis; D002460:Cell Line / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation; D006526:Hepatitis C / Q000150:complications / Q000276:immunology* / Q000473:pathology; D019698:Hepatitis C, Chronic / Q000150:complications / Q000276:immunology / Q000473:pathology; D022781:Hepatocytes / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D037181:Lectins, C-Type / Q000032:analysis; D008099:Liver / Q000276:immunology* / Q000473:pathology; D008103:Liver Cirrhosis / Q000209:etiology / Q000276:immunology / Q000473:pathology; D018448:Models, Immunological; D055651:NK Cell Lectin-Like Receptor Subfamily B; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014162:Transfection
chemical_list: D018949:Antigens, CD1; D055610:Antigens, CD1d; D000954:Antigens, Surface; C526877:CD1D protein, human; D019002:CD56 Antigen; D018793:Interleukin-13; C527203:KLRB1 protein, human; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D007371:Interferon-gamma