Brief Report: CD14brightCD16- monocytes and sCD14 level negatively associate with CD4-memory T-cell frequency and predict HCV-decline on therapy.
During HIV+ hepatitis C virus (HCV)+ coinfection CD14CD16 monocytes produce soluble immune-activation markers that predict disease progression and poor response to interferon (IFN)-α treatment. We evaluated relationships among immune activation, monocyte phenotype, CD4-memory T cells, and HCV-, cytomegalovirus-, and cytomegalovirus/Epstein-Barr virus/influenza-specific IFN-γ-response before and during IFN-α treatment. Effector-memory and central-memory CD4 T-cell frequencies were lower in HCV+ HIV+ donors than in uninfected donors and correlated negatively with HCV level, CD14CD16 monocytes, and plasma sCD14. sCD14 and CD14CD16 monocytes negatively correlated with IFN-α-dependent HCV decline. CD4 effector-memory T cells positively associated with cytomegalovirus/Epstein-Barr virus/influenza(CEF)-specific IFN-γ response, while sCD14 negatively associated with both CD4 effector-memory T cells and CEF-specific IFN-γ response. These data support a role for memory-CD4 T cells in HCV containment and link immune activation and CD14CD16-monocyte frequency to the failure of IFN-dependent HCV clearance.
*Department of Pathology, The Cleveland VA Medical Center, Case Western Reserve University, Cleveland, OH; †Center for Infection Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden; ‡School of Health and Rehabilitation Sciences, Division of Medical Laboratory Science, The Ohio State University, Columbus, OH; §University of Cincinnati Medical Center, Cincinnati, OH; ‖Weill Cornell Medical College, New York, NY; ¶Hamd Healthcare Quality Institute and Hamad Medical Corporation, Doha, Qatar; #Harvard T.H. Chan School of Public Health, Boston, MA, USA **Rush University Medical Center, Chicago, IL; and ††Department of Medicine, University Hospitals Case Medical Center, and the Center for AIDS Research, Cleveland, OH.
Chelsey J
CJ
Judge
Johan K
JK
Sandberg
Nicholas T
NT
Funderburg
Kenneth E
KE
Sherman
Adeel A
AA
Butt
Minhee
M
Kang
Alan L
AL
Landay
Michael M
MM
Lederman
Donald D
DD
Anthony
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D060085:Coinfection / Q000276:immunology*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D016174:Hepacivirus / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects / Q000276:immunology*; D007372:Interferons / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D012254:Ribavirin / Q000627:therapeutic use; D055815:Young Adult
D000998:Antiviral Agents; D018950:Lipopolysaccharide Receptors; D012254:Ribavirin; D007372:Interferons