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Cytokine profiles, CTL response and T cell frequencies in the peripheral blood of acute patients and individuals recovered from hepatitis E infection.

Tripathy AS, Das R, Rathod SB, Arankalle VA - PLoS ONE (2012)

Bottom Line: Comparisons of cytokines/chemokines revealed significantly high levels of IL-1α and sIL-2Rα during acute phase.Circulating peripheral CD4/CD8+ T-cell subsets in acute and recovered individuals were comparable compared to controls, while among patient categories CD8+T cell subset was significantly higher in recovered individuals.Lack of robust HEV ORF2-specific CTL response in the peripheral blood of HEV infected patients during the acute and recovered phases of the disease may be associated with involvement of innate immune cells/localization of the immune events at the site of infection.

View Article: PubMed Central - PubMed

Affiliation: Hepatitis Group, National Institute of Virology, Pune, India. anuradhastripathy@hotmail.com

ABSTRACT

Background: Hepatitis E is a major public health problem in the developing countries. Pathogenesis of hepatitis E virus (HEV) infection is poorly understood.

Methods: This case-control study included 124 Hepatitis E patients (46 acute and 78 recovered), 9 with prior exposure to HEV and 71 anti-HEV negative healthy controls. HEV induced CTL response by Elispot, cytokines/chemokines quantitation by Milliplex assay and peripheral CD4+ & CD8+ T cell frequencies by flow cytometry were assessed.

Results: Among the patient categories, HEV specific IFN-γ responses as recorded by Elispot were comparable. Comparisons of cytokines/chemokines revealed significantly high levels of IL-1α and sIL-2Rα during acute phase. Circulating peripheral CD4/CD8+ T-cell subsets in acute and recovered individuals were comparable compared to controls, while among patient categories CD8+T cell subset was significantly higher in recovered individuals.

Conclusions: Our findings suggest that IL-1α and sIL-2Rα play a role in the pathogenesis of acute Hepatitis E infection. Lack of robust HEV ORF2-specific CTL response in the peripheral blood of HEV infected patients during the acute and recovered phases of the disease may be associated with involvement of innate immune cells/localization of the immune events at the site of infection.

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IFN-γ responses by Elispot in Hepatitis E patients and controls.Scatter plot showing Hepatitis E antigen specific IFN-γ responses in different groups. A) IgG anti HEV negative/HEV naive, n = 18 B) IgG anti HEV positive/HEV exposed, n = 9, C) AVH-E, n = 27 and D) Recovered individuals from hepatitis E, n = 22. PBMCs were isolated from all subjects mentioned and were cultured with recombinant ORF2 protein in-vitro. IFN-γ secreting cell frequencies were determined by Elispot assay. The figures in parentheses show the number of SFCs per105 cells.
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pone-0031822-g001: IFN-γ responses by Elispot in Hepatitis E patients and controls.Scatter plot showing Hepatitis E antigen specific IFN-γ responses in different groups. A) IgG anti HEV negative/HEV naive, n = 18 B) IgG anti HEV positive/HEV exposed, n = 9, C) AVH-E, n = 27 and D) Recovered individuals from hepatitis E, n = 22. PBMCs were isolated from all subjects mentioned and were cultured with recombinant ORF2 protein in-vitro. IFN-γ secreting cell frequencies were determined by Elispot assay. The figures in parentheses show the number of SFCs per105 cells.

Mentions: To characterize the antigen-specific T-cell response to HEV, we determined the frequency of IFN-γ-producing T cells in response to rORF2p by ELISPOT assay (Figure 1). In control/HEV naïve group (IgM/IgG anti HEV negative) (n = 18), IFN-γ responses in unstimulated, rORF2p and PHA stimulated cells were 0(0–4), 1(0–25) and 10-4(12–248) SFC/105 cells respectively (Figure 1A). The corresponding figures in the exposed group (IgM anti-HEV negative and IgG anti HEV positive) (n = 9) were 0(0–6), 4(0–16) and 107(10–196) respectively (Figure 1B).


Cytokine profiles, CTL response and T cell frequencies in the peripheral blood of acute patients and individuals recovered from hepatitis E infection.

Tripathy AS, Das R, Rathod SB, Arankalle VA - PLoS ONE (2012)

IFN-γ responses by Elispot in Hepatitis E patients and controls.Scatter plot showing Hepatitis E antigen specific IFN-γ responses in different groups. A) IgG anti HEV negative/HEV naive, n = 18 B) IgG anti HEV positive/HEV exposed, n = 9, C) AVH-E, n = 27 and D) Recovered individuals from hepatitis E, n = 22. PBMCs were isolated from all subjects mentioned and were cultured with recombinant ORF2 protein in-vitro. IFN-γ secreting cell frequencies were determined by Elispot assay. The figures in parentheses show the number of SFCs per105 cells.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3285172&req=5

pone-0031822-g001: IFN-γ responses by Elispot in Hepatitis E patients and controls.Scatter plot showing Hepatitis E antigen specific IFN-γ responses in different groups. A) IgG anti HEV negative/HEV naive, n = 18 B) IgG anti HEV positive/HEV exposed, n = 9, C) AVH-E, n = 27 and D) Recovered individuals from hepatitis E, n = 22. PBMCs were isolated from all subjects mentioned and were cultured with recombinant ORF2 protein in-vitro. IFN-γ secreting cell frequencies were determined by Elispot assay. The figures in parentheses show the number of SFCs per105 cells.
Mentions: To characterize the antigen-specific T-cell response to HEV, we determined the frequency of IFN-γ-producing T cells in response to rORF2p by ELISPOT assay (Figure 1). In control/HEV naïve group (IgM/IgG anti HEV negative) (n = 18), IFN-γ responses in unstimulated, rORF2p and PHA stimulated cells were 0(0–4), 1(0–25) and 10-4(12–248) SFC/105 cells respectively (Figure 1A). The corresponding figures in the exposed group (IgM anti-HEV negative and IgG anti HEV positive) (n = 9) were 0(0–6), 4(0–16) and 107(10–196) respectively (Figure 1B).

Bottom Line: Comparisons of cytokines/chemokines revealed significantly high levels of IL-1α and sIL-2Rα during acute phase.Circulating peripheral CD4/CD8+ T-cell subsets in acute and recovered individuals were comparable compared to controls, while among patient categories CD8+T cell subset was significantly higher in recovered individuals.Lack of robust HEV ORF2-specific CTL response in the peripheral blood of HEV infected patients during the acute and recovered phases of the disease may be associated with involvement of innate immune cells/localization of the immune events at the site of infection.

View Article: PubMed Central - PubMed

Affiliation: Hepatitis Group, National Institute of Virology, Pune, India. anuradhastripathy@hotmail.com

ABSTRACT

Background: Hepatitis E is a major public health problem in the developing countries. Pathogenesis of hepatitis E virus (HEV) infection is poorly understood.

Methods: This case-control study included 124 Hepatitis E patients (46 acute and 78 recovered), 9 with prior exposure to HEV and 71 anti-HEV negative healthy controls. HEV induced CTL response by Elispot, cytokines/chemokines quantitation by Milliplex assay and peripheral CD4+ & CD8+ T cell frequencies by flow cytometry were assessed.

Results: Among the patient categories, HEV specific IFN-γ responses as recorded by Elispot were comparable. Comparisons of cytokines/chemokines revealed significantly high levels of IL-1α and sIL-2Rα during acute phase. Circulating peripheral CD4/CD8+ T-cell subsets in acute and recovered individuals were comparable compared to controls, while among patient categories CD8+T cell subset was significantly higher in recovered individuals.

Conclusions: Our findings suggest that IL-1α and sIL-2Rα play a role in the pathogenesis of acute Hepatitis E infection. Lack of robust HEV ORF2-specific CTL response in the peripheral blood of HEV infected patients during the acute and recovered phases of the disease may be associated with involvement of innate immune cells/localization of the immune events at the site of infection.

Show MeSH
Related in: MedlinePlus