Hepatitis C virus-induced secretion of inflammatory chemokines preferentially recruits NKG2A+CD8+ T cells.
In patients with hepatitis C, a loss-of-function mutation of chemokine receptor CCR5 (CCR5Delta32) has been shown to be associated with spontaneous viral clearance and lower levels of hepatic inflammation. In the present study, we show that CCR5 is coexpressed with the inhibitory NKG2A receptor on CD8(+) T cells. Consequently, CCR5(+) T cells were highly susceptible to NKG2A-mediated inhibition of cytotoxic activity and NKG2A(+) lymphocytes were preferentially attracted by CCR5 ligands induced by hepatitis C virus E2 antigen. Thus, CCR5 is likely to exert immunoregulatory effects in hepatitis C virus infection by preferentially recruiting CD8(+) T cells bearing the inhibitory NKG2A receptor to the liver.
Nattermann
Jacob
J
Department of Internal Medicine I, University of Bonn, Germany. Jacob.Nattermann@ukbuni-bonn.de
Sherzada
Roman
R
Iwan
Agathe
A
Bogen
Dominik
D
Niederle
Ina Maria
IM
Schulte
Daniela
D
Mertens
Eva
E
Nischalke
Hans Dieter
HD
Krämer
Benjamin
B
Sauerbruch
Tilman
T
Leifeld
Ludger
L
Spengler
Ulrich
U
D000071443:12E7 Antigen; D015703:Antigens, CD / Q000276:immunology; D019002:CD56 Antigen / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000276:immunology; D018925:Chemokines / Q000378:metabolism*; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D006526:Hepatitis C / Q000276:immunology* / Q000503:physiopathology*; D006801:Humans; D007249:Inflammation / Q000821:virology*; D007694:Killer Cells, Natural / Q000276:immunology; D055654:NK Cell Lectin-Like Receptor Subfamily C; D012367:RNA, Viral / Q000097:blood; D019713:Receptors, CCR5 / Q000276:immunology; D011971:Receptors, Immunologic / Q000276:immunology*; D055607:Receptors, Natural Killer Cell; D012016:Reference Values; D014758:Viral Core Proteins / Q000276:immunology
D000071443:12E7 Antigen; D015703:Antigens, CD; D019002:CD56 Antigen; C061828:CD99 protein, human; D015815:Cell Adhesion Molecules; D018925:Chemokines; C527054:KLRC1 protein, human; D055654:NK Cell Lectin-Like Receptor Subfamily C; D012367:RNA, Viral; D019713:Receptors, CCR5; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D014758:Viral Core Proteins