[Immunology of HCV infection: the causes of impaired cellular immune response and the effect of antiviral treatment].
BACKGROUND
The outcome of HCV infection and the response to antiviral treatment depend on both viral and host factors. Host immune response contributes not only to viral control, clinical recovery and protective immunity, but also to chronic hepatitis and liver cirrhosis. Establishing immunological status and identifying pretreatment immunological factors associated with better response to therapy might be of importance in the understanding of the successful immune response and in the future of combination therapy to HCV infection.


OBJECTIVE
The authors delivered a review on the immunology of HCV infection and characterized the cause of impaired cellular immune response in chronic HCV infection. Natural killer (NK) cell activity, perforin and the inhibitory CD81 HCV co-receptor expression, and Th1/Th2 cytokine production of the monocytes and lymphocytes have been investigated.


METHODS
42 patients with chronic hepatitis C, out of them 25 being on interferon (PEG-IFN) + ribavirin (RBV) therapy, 12 sustained virological responders, 26 HCV carriers with normal transaminase values and 22 healthy controls were studied. NK cell activity, perforin and CD81 expression, the IFNgamma, TNFalpha, IL-2 (Th1) and IL-4, IL-6, IL-10 (Th2) production of LPS stimulated monocytes and PMA + ionomycine stimulated lymphocytes were measured by flow-cytometry.


RESULTS
In patients with chronic hepatitis C we demonstrated decreased NK cell activity associated with increased CD81 expression. The perforin expression of lymphocytes was also impaired in HCV patients. The pretreatment capacity of the macrophages to produce TNFalpha was predictive for sustained virological response. This increased TNFalpha production of the monocytes counteracted the observed impaired Th1 type cytokine production of the lymphocytes. IL-10 and IL-4 production showed positive correlation with HCV RNA levels, and negative correlation with histological activity index was noted. PEG-IFN + RBV treatment increased NK activity, perforin expression, Th1 type cytokine production of thr lymphocytes and downregulated CD81 expression inducing effective cellular immune response against HCV. The author's results provide further data to understand the causes of impaired cellular immune response in chronic HCV hepatitis and may be useful in the developement of immunotherapy as an adjunctive treatment to cure patients with chronic hepatitis C.
Pár
Gabriella
G
Pécs Tudományegyetem, Altalános Orvostudományi Kar, I. Belgyógyászati Klinika.
Berki
Tímea
T
Pálinkás
László
L
Balogh
Péter
P
Szereday
László
L
Halász
Melinda
M
Szekeres-Barthó
Júlia
J
Miseta
Attila
A
Hegedus
Géza
G
Mózsik
Gyula
G
Hunyady
Béla
B
Pár
Alajos
A
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D000998:Antiviral Agents / Q000627:therapeutic use*; D016207:Cytokines / Q000378:metabolism*; D004279:DNA, Viral / Q000302:isolation & purification; D004359:Drug Therapy, Combination; D005260:Female; D005434:Flow Cytometry; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification; D006526:Hepatitis C / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D007371:Interferon-gamma / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D054353:Perforin; D011092:Polyethylene Glycols; D052899:Pore Forming Cytotoxic Proteins; D012367:RNA, Viral / Q000302:isolation & purification; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use; D060225:Tetraspanin 28; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015703:Antigens, CD; D000998:Antiviral Agents; C554798:CD81 protein, human; D016207:Cytokines; D004279:DNA, Viral; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007378:Interleukins; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D012367:RNA, Viral; D011994:Recombinant Proteins; D060225:Tetraspanin 28; D014409:Tumor Necrosis Factor-alpha; D054353:Perforin; D011092:Polyethylene Glycols; D012254:Ribavirin; D007371:Interferon-gamma; C417083:peginterferon alfa-2b