Limits...
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.

Show MeSH

Related in: MedlinePlus

example of proliferation for PBMC of volunteer EFS 20. 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 or CEF antigens. The positive responses are in bold characters.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3369207&req=5

Figure 1: example of proliferation for PBMC of volunteer EFS 20. 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 or CEF antigens. The positive responses are in bold characters.

Mentions: HCV-specific proliferative T cell responses were tested in 62 of the 65 uninfected volunteers (UI). Among these, 2 were positive for Core, and 4 for NS3 (Table 1). The response directed against Core involved both CD4 and CD8 populations for volunteer EFS20 who had no known risk of HCV exposure (Figure 1, panels A & B, and Table 2), and a CD4 population for EFS 11 (at risk) (Table 3). For NS3, a response involved the CD4 population (COC 13, Table 2, and EFS14, Table 3), the CD8 population (EFS 21, Table 3) or both CD4 and CD8 populations (EFS 24, Table 3). All three EFS donors were at risk of HCV exposure, in contrast to risk-free volunteer COC 13. None of the supposedly uninfected (UI) volunteers was found to be positive for both NS3 and Core.


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 volunteer EFS 20. 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 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 1: example of proliferation for PBMC of volunteer EFS 20. 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 or CEF antigens. The positive responses are in bold characters.
Mentions: HCV-specific proliferative T cell responses were tested in 62 of the 65 uninfected volunteers (UI). Among these, 2 were positive for Core, and 4 for NS3 (Table 1). The response directed against Core involved both CD4 and CD8 populations for volunteer EFS20 who had no known risk of HCV exposure (Figure 1, panels A & B, and Table 2), and a CD4 population for EFS 11 (at risk) (Table 3). For NS3, a response involved the CD4 population (COC 13, Table 2, and EFS14, Table 3), the CD8 population (EFS 21, Table 3) or both CD4 and CD8 populations (EFS 24, Table 3). All three EFS donors were at risk of HCV exposure, in contrast to risk-free volunteer COC 13. None of the supposedly uninfected (UI) volunteers was found to be positive for both NS3 and Core.

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