Immune responses to hepatitis C and non-hepatitis C antigens in hepatitis C virus infected and HIV-1 coinfected patients.
OBJECTIVE
To characterize immune phenotype and function in hepatitis C virus (HCV) infection in the presence and absence of HIV-1 infection.


METHODS
Cross-sectional comparison among controls (group A), patients with HCV infection (group B), HCV-HIV-1 coinfected patients (group C), coinfected patients receiving treatment for HIV-1 (group D), and untreated HIV-1 infected patients (group E).


METHODS
Flow cytometric analysis for lymphocyte phenotypes, lymphocyte proliferation and cytokine production by ELISPOT.


RESULTS
HCV infected patients tended to have an increased percentage of activated (CD38, HLA-DR) CD8 cells (group A, 2+/-1.4%; group B, 6+/-3.9%; P=0.08). Proliferative responses to non-HCV antigens were comparable in group A and group B subjects. A greater proportion of group B patients had stimulation indices (SI) > 3 to the HCV protein NS3 compared to group C and D patients (67%, 0%, and 11% respectively; P < 0.003), but only two patients in group B had SI > or = 5. The SI to NS3 was significantly higher in group B patients [median, 4; interquartile range (IQR), 3-9) than in group C (median, 2; IQR, 1-3; P < 0.04) or group D (median, 1; IQR, 1-4; P < 0.009) patients. Plasma HCV RNA levels correlated directly with alanine aminotransferase levels (p, 0.52; P < 0.05) and inversely with the number of CD4 lymphocytes (rho, -0.55; P < 0.009) and proliferation to NS3 (p, -0.55; P < 0.009).


CONCLUSIONS
Lymphocytes of HCV infected patients show weak proliferative responses to HCV antigens while responses to other antigens are preserved. Infection with HIV-1 potentiates this deficiency. Poor CD4 T cell responses to HCV are associated with and may determine the failure to control HCV propagation.
Valdez
H
H
Case Western Reserve University, Cleveland, Ohio, USA.
Anthony
D
D
Farukhi
F
F
Patki
A
A
Salkowitz
J
J
Heeger
P
P
Peterson
D L
DL
Post
A B
AB
Asaad
R
R
Lederman
M M
MM
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000276:immunology*; D015497:HIV-1; D018963:Hepatitis Antigens / Q000276:immunology*; D006526:Hepatitis C / Q000150:complications / Q000276:immunology*; D018936:Hepatitis C Antigens / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010641:Phenotype
D018963:Hepatitis Antigens; D018936:Hepatitis C Antigens