Cutting edge: Compartmentalization of Th1-like noninvariant CD1d-reactive T cells in hepatitis C virus-infected liver.
Murine intrahepatic lymphocytes (IHL) are dominated by invariant TCR alpha-chain expressing CD1d-reactive NKT cells, which can cause model hepatitis. Invariant NKT (CD56(+/-)CD161(+)) and recently identified noninvariant CD1d-reactive T cells rapidly produce large amounts of IL-4 and/or IFN-gamma and can regulate Th1/Th2 responses. Human liver contains large numbers of CD56(+) NKT cells but few invariant NKT. Compared with matched peripheral blood T cell lines, primary IHL lines from patients with chronic hepatitis C had high levels of CD161 and CD1d reactivity, but the invariant TCR was rare. CD1d-reactive IHL were strikingly Th1 biased. IHL also demonstrated CD1d-specific cytotoxic activity. Hepatocytes and other liver cells express CD1d. These results identify a novel population of human T cells that could contribute to destructive as well as protective immune responses in the liver. CD1d-reactive T cells may have distinct roles in different tissues.
Exley
Mark A
MA
Cancer Biology Program, Department of Medicine, Beth Israel-Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. mexley@bidmc.harvard.edu
He
Qi
Q
Cheng
Olivia
O
Wang
Ruo-Jie
RJ
Cheney
Catherine P
CP
Balk
Steven P
SP
Koziel
Margaret J
MJ
D018949:Antigens, CD1 / Q000378:metabolism*; D055610:Antigens, CD1d; D000954:Antigens, Surface / Q000032:analysis; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D003601:Cytotoxicity Tests, Immunologic; D006526:Hepatitis C / Q000276:immunology* / Q000821:virology; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology; D037181:Lectins, C-Type; D008099:Liver / Q000276:immunology / Q000821:virology; D008213:Lymphocyte Activation; D055651:NK Cell Lectin-Like Receptor Subfamily B; D016176:T-Lymphocyte Subsets / Q000145:classification / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*
D018949:Antigens, CD1; D055610:Antigens, CD1d; D000954:Antigens, Surface; C526877:CD1D protein, human; D016207:Cytokines; C527203:KLRB1 protein, human; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D007371:Interferon-gamma