Antigen-specific cytokine response to hepatitis C virus core epitopes in HIV/hepatitis C virus-coinfected patients.
OBJECTIVE
Epidemiological data indicate that hepatitis C virus (HCV) infection runs a more rapid and severe course of disease in HIV-coinfected patients, probably because of an altered immune response.


METHODS
We investigated whether HCV-specific cytokine responses are affected by HIV coinfection.


METHODS
Using triple colour flow cytometry on peripheral blood lymphocytes after stimulation with the four major immunodominant HCV core T cell epitopes, CT1-CT4, we determined intracytoplasmic production of IFN-gamma, IL-2, IL-4, IL-10 and CD30 expression, a putative surrogate marker of type 2 cells. Fifteen patients with asymptomatic HIV/HCV coinfection (group A), 15 patients with chronic HCV infection (group B) and 10 HIV-infected patients without hepatitis C (group C) were included in the study.


RESULTS
In group A, HCV antigens induced significantly higher IL-2 and IFN-gamma production than groups B and C (P < 0.05). Groups A and B showed a similar induction of CD30, which was significantly higher than in group C (P < 0.001). Remarkably, in group A HCV antigens induced IL-4 production in addition to IL-10 and IFN-gamma in the CD30 subset, whereas in groups B and C no IL-4 induction was observed in this T cell subset (P < 0.002).


CONCLUSIONS
Our data suggest that asymptomatic HIV coinfection importantly alters the HCV-specific cytokine response towards a greater production of proinflammatory type 1 cytokines. Moreover, the antiviral activity of type 1 cytokines may be modified by an increased production of type 2 cytokines in the CD30 subset. The altered cytokine pattern may contribute to the adverse natural course of hepatitis C in HIV coinfection.
Woitas
R P
RP
Department of Internal Medicine I, University of Bonn, Germany. woitas@uni-bonn.de
Rockstroh
J K
JK
Beier
I
I
Jung
G
G
Kochan
B
B
Matz
B
B
Brackmann
H H
HH
Sauerbruch
T
T
Spengler
U
U
D000328:Adult; D000368:Aged; D017252:CD3 Complex / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis* / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000150:complications* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000502:physiology; D016174:Hepacivirus / Q000235:genetics / Q000502:physiology; D006526:Hepatitis C / Q000150:complications* / Q000276:immunology / Q000821:virology; D018936:Hepatitis C Antigens / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes; D017730:Ki-1 Antigen / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D013601:T-Lymphocytes / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014758:Viral Core Proteins / Q000276:immunology
D017252:CD3 Complex; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D018936:Hepatitis C Antigens; D016056:Immunodominant Epitopes; D017730:Ki-1 Antigen; D012367:RNA, Viral; D014758:Viral Core Proteins