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Hepatitis C virus-specific cellular immune responses in individuals with no evidence of infection.

Rivière Y, Montange T, Janvier G, Marnata C, Durrieu L, Chaix ML, Isaguliants M, Launay O, Bresson JL, Pol S - Virol. J. (2012)

Bottom Line: Uninfected volunteers (n = 20) with a chronically HCV-infected partner were included as positive controls for potential exposure to HCV and HCV infection, respectively.A pool of unrelated peptides was used as a negative control, and a peptide mix of human cytomegalovirus, Epstein-Bar virus and Influenza virus as a positive control.Overall, 20% of presumably HCV-uninfected subject tested had detectable T-cell responses to the virus, a rate much higher than previous estimates of HCV prevalence in developed countries.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratoire d'Immunopathologie Virale, Institut Pasteur; and CNRS URA 3015, 25 rue du Dr Roux, 75015 Paris, France. yves.riviere@pasteur.fr

ABSTRACT
The detection of hepatitis C virus (HCV)-specific T cell responses in HCV-uninfected, presumably unexposed, subjects could be due to an underestimation of the frequency of spontaneously resolving infections, as most acute HCV infections are clinically silent. To address this hypothesis, HCV-specific cellular immune responses were characterized, in individuals negative for an HCV PCR assay and humoral response, with (n = 32) or without (n = 33) risk of exposure to HCV. Uninfected volunteers (n = 20) with a chronically HCV-infected partner were included as positive controls for potential exposure to HCV and HCV infection, respectively. HCV-specific T cell responses in freshly isolated peripheral blood mononuclear cells were studied ex vivo by ELISPOT and CFSE-based proliferation assays using panels of HCV Core and NS3-derived peptides. A pool of unrelated peptides was used as a negative control, and a peptide mix of human cytomegalovirus, Epstein-Bar virus and Influenza virus as a positive control. Overall, 20% of presumably HCV-uninfected subject tested had detectable T-cell responses to the virus, a rate much higher than previous estimates of HCV prevalence in developed countries. This result would be consistent with unapparent primary HCV infections that either cleared spontaneously or remained undetected by conventional serological assays.

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example of proliferation for PBMC of the chronically infected CIC 38 volunteer. Dot-plots show the percentage of proliferative CD8 + (FL1/FL4) or CD4 + (FL1/FL5) - T cells. The number in the upper left panel stands for the percentage of CD4+ or CD8+ proliferative cells among the total CD4+ or CD8+ -T lymphocyte population, respectively, in the absence (DMSO) or the presence of Core, NS3 or CEF antigens. The positive responses are in bold characters.
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Figure 2: example of proliferation for PBMC of the chronically infected CIC 38 volunteer. Dot-plots show the percentage of proliferative CD8 + (FL1/FL4) or CD4 + (FL1/FL5) - T cells. The number in the upper left panel stands for the percentage of CD4+ or CD8+ proliferative cells among the total CD4+ or CD8+ -T lymphocyte population, respectively, in the absence (DMSO) or the presence of Core, NS3 or CEF antigens. The positive responses are in bold characters.

Mentions: In the group of chronically infected patients (CI) 17 patients were tested (Table 1), and three showed a Core-specific response: one (CIC 34) involving the CD8 population and two (CIC 38, 46) the CD4 population (Table 4, and Figure 2, panel A). For NS3, 2/16 patients were positive: one involving CD8 cells (CIC18), and one CD4 (CIC 38) (Table 4, and Figure 2 panel C). Thus one patient (CIC 38) was positive for both NS3 and Core, in both cases the response involving the CD4 population.


Hepatitis C virus-specific cellular immune responses in individuals with no evidence of infection.

Rivière Y, Montange T, Janvier G, Marnata C, Durrieu L, Chaix ML, Isaguliants M, Launay O, Bresson JL, Pol S - Virol. J. (2012)

example of proliferation for PBMC of the chronically infected CIC 38 volunteer. Dot-plots show the percentage of proliferative CD8 + (FL1/FL4) or CD4 + (FL1/FL5) - T cells. The number in the upper left panel stands for the percentage of CD4+ or CD8+ proliferative cells among the total CD4+ or CD8+ -T lymphocyte population, respectively, in the absence (DMSO) or the presence of Core, NS3 or CEF antigens. The positive responses are in bold characters.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3369207&req=5

Figure 2: example of proliferation for PBMC of the chronically infected CIC 38 volunteer. Dot-plots show the percentage of proliferative CD8 + (FL1/FL4) or CD4 + (FL1/FL5) - T cells. The number in the upper left panel stands for the percentage of CD4+ or CD8+ proliferative cells among the total CD4+ or CD8+ -T lymphocyte population, respectively, in the absence (DMSO) or the presence of Core, NS3 or CEF antigens. The positive responses are in bold characters.
Mentions: In the group of chronically infected patients (CI) 17 patients were tested (Table 1), and three showed a Core-specific response: one (CIC 34) involving the CD8 population and two (CIC 38, 46) the CD4 population (Table 4, and Figure 2, panel A). For NS3, 2/16 patients were positive: one involving CD8 cells (CIC18), and one CD4 (CIC 38) (Table 4, and Figure 2 panel C). Thus one patient (CIC 38) was positive for both NS3 and Core, in both cases the response involving the CD4 population.

Bottom Line: Uninfected volunteers (n = 20) with a chronically HCV-infected partner were included as positive controls for potential exposure to HCV and HCV infection, respectively.A pool of unrelated peptides was used as a negative control, and a peptide mix of human cytomegalovirus, Epstein-Bar virus and Influenza virus as a positive control.Overall, 20% of presumably HCV-uninfected subject tested had detectable T-cell responses to the virus, a rate much higher than previous estimates of HCV prevalence in developed countries.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratoire d'Immunopathologie Virale, Institut Pasteur; and CNRS URA 3015, 25 rue du Dr Roux, 75015 Paris, France. yves.riviere@pasteur.fr

ABSTRACT
The detection of hepatitis C virus (HCV)-specific T cell responses in HCV-uninfected, presumably unexposed, subjects could be due to an underestimation of the frequency of spontaneously resolving infections, as most acute HCV infections are clinically silent. To address this hypothesis, HCV-specific cellular immune responses were characterized, in individuals negative for an HCV PCR assay and humoral response, with (n = 32) or without (n = 33) risk of exposure to HCV. Uninfected volunteers (n = 20) with a chronically HCV-infected partner were included as positive controls for potential exposure to HCV and HCV infection, respectively. HCV-specific T cell responses in freshly isolated peripheral blood mononuclear cells were studied ex vivo by ELISPOT and CFSE-based proliferation assays using panels of HCV Core and NS3-derived peptides. A pool of unrelated peptides was used as a negative control, and a peptide mix of human cytomegalovirus, Epstein-Bar virus and Influenza virus as a positive control. Overall, 20% of presumably HCV-uninfected subject tested had detectable T-cell responses to the virus, a rate much higher than previous estimates of HCV prevalence in developed countries. This result would be consistent with unapparent primary HCV infections that either cleared spontaneously or remained undetected by conventional serological assays.

Show MeSH
Related in: MedlinePlus