Reduced CC chemokine receptor (CCR) 1 and CCR5 surface expression on peripheral blood T lymphocytes from patients with chronic hepatitis C infection.
T cell recruitment to the infected liver is an essential step for the efficient elimination of hepatitis viruses. The surface expression of CC chemokine receptor (CCR) 1, CCR4, and CCR5 on peripheral blood T lymphocytes and their responsiveness to the chemokines macrophage inflammatory proteins (MIP)-1alpha, MIP-1beta, and RANTES (regulated on activation, normally T cell-expressed and secreted) was analyzed in patients with chronic hepatitis C and hepatitis B infection and compared with healthy subjects. Although CCR4 surface expression was not altered, hepatitis C virus (HCV)-infected patients had lower proportions of CD8 T cells with CCR1 and CCR5 surface expression (P<.05). Migration of CD8 T cells in response to MIP-1alpha, MIP-1beta, and RANTES was significantly reduced in HCV-infected patients (P<.05). Intracellular CCR1 and CCR5 protein and messenger RNA levels in peripheral blood T cells did not indicate reduced chemokine receptor biosynthesis in hepatitis C infection. Thus, chronic hepatitis C, but not hepatitis B, infection alters surface expression of distinct CCRs, resulting in lower CC chemokine responsiveness.
Lichterfeld
Mathias
M
Department of General Internal Medicine, Rheinische Friedrich Wilhelms Universität, Sigmund-Freud-Strasse 25, D-53105 Bonn, Germany. m.lichterfeld@gmx.net
Leifeld
Ludger
L
Nischalke
Hans Dieter
HD
Rockstroh
Jürgen K
JK
Hess
Lothar
L
Sauerbruch
Tilman
T
Spengler
Ulrich
U
D000328:Adult; D000368:Aged; D016516:CD4-CD8 Ratio; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000494:pharmacology; D003430:Cross-Sectional Studies; D005260:Female; D005434:Flow Cytometry; D019698:Hepatitis C, Chronic / Q000097:blood*; D006801:Humans; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D054389:Receptors, CCR1; D054398:Receptors, CCR4; D019713:Receptors, CCR5 / Q000096:biosynthesis*; D019707:Receptors, Chemokine / Q000096:biosynthesis*; D013499:Surface Properties; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism* / Q000821:virology
C515300:CCR1 protein, human; C515354:CCR4 protein, human; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D054389:Receptors, CCR1; D054398:Receptors, CCR4; D019713:Receptors, CCR5; D019707:Receptors, Chemokine