Decrease in CD3-negative-CD8dim(+) and Vdelta2/Vgamma9 TcR+ peripheral blood lymphocyte counts, low perforin expression and the impairment of natural killer cell activity is associated with chronic hepatitis C virus infection.
OBJECTIVE
As chronic hepatitis C virus (HCV) infection is associated with impaired natural killer (NK) cell cytotoxicity, we examined the phenotypes and perforin expression of peripheral blood lymphocytes, as well as the effect of interferon-alpha2b (IFN-alpha2b) therapy.


METHODS
Thirty-three patients had chronic hepatitis C, and of them 12 had been on IFN-alpha2b treatment. Eleven individuals had been treated earlier with IFN-alpha2b and completely cured, and eight were HCV carriers with persistently normal serum alanine aminotransferase. Three-colour flow cytometry was used to measure the percentage of CD3(+/-)CD8+, CD3+CD4+, gammadeltaTcR+, Vdelta2 TcR+, Vgamma9 TcR+, Vdelta1 TcR+, CD3-CD16+, CD3-CD56+, CD19+ and perforin-positive cells. NK cell activity was assessed by single cell cytotoxic and flow cytometric assay.


RESULTS
Patients with chronic hepatitis C showed an impaired NK cytotoxicity, decreased percentage of CD3-negative-CD8dim-positive (NK subtype) and Vgamma9/Vdelta2 TcR+ as well as perforin-positive T lymphocytes, compared to controls and to those who were cured from HCV infection. IFN-alpha2b increased NK cell cytotoxicity and the percentage of perforin-positive lymphocytes.


CONCLUSIONS
Our findings suggest that in chronic HCV infection a decreased percentage of CD3(-)CD8+, Vgamma9/Vdelta2 TcR+ and perforin-positive T cells and simultaneous decreased peripheral NK activity may contribute to the impaired cellular immune response and the chronicity of the disease.
Pár
Gabriella
G
Institute of Microbiology and Immunology, University of Pécs, Pécs, Hungary
Rukavina
Daniel
D
Podack
Eckhard R
ER
Horányi
Margit
M
Szekeres-Barthó
Júlia
J
Hegedüs
Géza
G
Paál
Mária
M
Szereday
László
L
Mózsik
Gyula
G
Pár
Alajos
A
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D017252:CD3 Complex / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D005260:Female; D005434:Flow Cytometry; D016694:Gene Rearrangement, delta-Chain T-Cell Antigen Receptor / Q000276:immunology; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000737:chemistry / Q000276:immunology* / Q000821:virology*; D018655:Lymphocyte Count; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis*; D008875:Middle Aged; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*; D011994:Recombinant Proteins
D000998:Antiviral Agents; D017252:CD3 Complex; D016827:CD8 Antigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011994:Recombinant Proteins; D054353:Perforin