Preservation of intrahepatic hepatitis C virus (HCV)-specific CD4+ T cell responses despite global loss of CD4+ T cells in HCV/HIV coinfection.
BACKGROUND
Human immunodeficiency virus (HIV) coinfection and low peripheral blood CD4(+) T cell counts are associated with increased hepatitis C liver disease.


METHODS
Hepatitis C virus (HCV)-specific CD4(+) T cell responses were assessed using interferon (IFN)- gamma enzyme-linked immunospot assays on peripheral blood mononuclear cells and expanded liver lymphocytes from HCV-monoinfected and HCV/HIV-coinfected subjects. Cell frequencies were determined using flow cytometry.


RESULTS
HIV coinfection was associated with decreased CD4(+) T cell percentages in both peripheral blood (21% vs. 48%; P<.0001) and liver (15% vs. 36%; P<.0001) and with reduced responsiveness of peripheral CD4(+) T cells to HCV antigens compared with HCV monoinfection (22% vs. 45%; P=.021). However, intrahepatic HCV-specific responses were maintained in HCV/HIV coinfection, compared with HCV monoinfection (38% vs. 32%; P=.7). Notably, the presence of HCV-specific responses was not related to the frequency of liver CD4(+) T cells (P=.4). Circulating and liver CD4(+) T cell percentages were correlated (r=0.58; P<.0001). Circulating percentages were also inversely associated with liver fibrosis stage among HCV/HIV-coinfected subjects (P=.029). Neither hepatic CD4(+) T cell percentages nor HCV-specific IFN- gamma responses in the liver or periphery predicted stage.


CONCLUSIONS
Despite decreases in peripheral blood HCV-specific CD4(+) T cell responses and intrahepatic CD4(+) T cell percentages, intrahepatic HCV-specific CD4(+) IFN- gamma responses were preserved in HCV/HIV coinfection.
Morishima
Chihiro
C
Department of Laboratory Medicine, University of Washington School of Medicine, Seattle, WA 98104, USA. chihiro@u.washington.edu
Shuhart
Margaret C
MC
Yoshihara
Christina S
CS
Paschal
Denise M
DM
Silva
Melissa A
MA
Thomassen
Lisa V
LV
Emerson
Scott S
SS
Gretch
David R
DR
D000956:Antigens, Viral; D001706:Biopsy; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006678:HIV; D015658:HIV Infections / Q000150:complications*; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000150:complications* / Q000276:immunology* / Q000473:pathology; D022781:Hepatocytes / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008099:Liver / Q000276:immunology* / Q000473:pathology; D008103:Liver Cirrhosis / Q000209:etiology* / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D037182:T-Cell Antigen Receptor Specificity
D000956:Antigens, Viral; D007371:Interferon-gamma