Features%20of%20immune%20status%20and%20immune%20response%20to%20HCV%20in%20healthy%20medical%20personal%20working%20in%20infectious%20disease%20hospital

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Features of immune status and immune response to
HCV in healthy medical personal working in
infectious disease hospital
Fedoseeva N.V. (1, 2), Shmeleva E.V. (1),
Kapitonova O. S. (1) Balmasova I.P. (1), Znoiko
O.O. (1), Yushchuk N.D.(1).   (1) Research
Institute of Medicine and Dentistry, Moscow State
University of Medicine and Dentistry, Moscow,
Russia (2) DI Ivanovsky Institute of Virology,
Ministry of Health and Social Welfare, Moscow,
Russia
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HCV-specific response in healthy individuals
detection and interpretation

• transient very mild infection/low-dose exposure,
  which was cleared
• 
  OR
  
• healthy carrier state or a sort of occult HCV
  infection with the virus being present in some
  body compartment
• (Margaret James Koziel et al. 1997, Paola
  Scognamiglio et al. 1999, Sanaa M. Kamal et al.
  2004, Maged Al-Sherbiny et al. 2005, Prem H.
  Thurairajah et al 2008, E. Mizukoshi et al.
  (2008) M. Zeremski et al. 2009, M. Bes et al.
  2009, A. Perrella et al. 2009, T. Hitziger et al.
  2009)
• activation of cross-reactive memory T-cells
  specific for other pathogens
• (Wedermeyer H. et al, 2001 Kennedy PT, Urbani S,
  Moses RA, Amadei B, Fisicaro P, et al. 2006.)

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Aim
Evaluation of strength, breadth, profile and
clinical importance of HCV-induced CD3 and
CD3-/CD56 proliferative responses in
seronegative aviremic health care workers
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Research objects

• Health care workers (doctors) 15
• Control group (healthy individuals) 9

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Research methods
Standard
Special methods PCR (hepatitis), immune status
(monoclonal staining), HCV-antibody testing
immune-enzyme analysis, flow cytometry based
proliferation (detection of ki67).
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The scheme of experiment (flow cytometry based
proliferation)
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Initial immune status and proliferative activity
of lymphocytes in two groups
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Proliferative capacity of PBMCs in response to
mitogen (PHA)
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Correlation dependence between cell populations
after incubation with PHA
CD4/ki67
CD3/ki67
CD8/ki67
CD56/ki67
CD3/FoxP3
healthcare workers
control group
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Proliferative activity of PBMCs in response to
HCV antigens
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Correlation dependence between cell populations
after incubation with HCV antigens
CoreNS4 1b genotype
NS4 2a3a genotype
CD4/ki67
CD4/ki67
CD3/ki67
CD3/ki67
CD8/ki67
CD8/ki67
CD56/ki67
CD3/FoxP3
CD56/ki67
CD3/FoxP3
healthcare workers
control group
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Proliferative activity of PBMCs in response to
HCV antigens. Indexes of proliferative activity.
IPA100(result-negative control)/negative
control 100

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Stimulation indexes for each person after
incubation with AG1 CoreNS4 1b
genotype SIresult/negative control
Control group
Healthcare workers
CD3/ki67 CD4/ki67
CD8/ki67 CD56/ki67
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Stimulation indexes for each person after
incubation with AG2 NS4 2a3a
genotypes SIresult/negative control
Control group
Healthcare workers
CD3/ki67 CD4/ki67
CD8/ki67 CD56/ki67
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Conclusions

• Suppression of cytotoxic lymphocytes activity
  was detected in healthcare workers group with
  vast spectrum of microbial antigen exposure
• This suppression didnt disappear after mitogen
  stimulation. Also after mitogen stimulation we
  detected reduction of NK proliferative activity
  and tendency to regulatory cells elevation
• Core and NS4 antigens of 1b genotype suppressed
  T-regulatory cells subpopulation, it was
  accompanied with reduction of CD8 cells and
  increasing of their proliferative activity and
  with decreasing of NK proliferative activity
• Incubation with NS4 antigens of 2a3a genotypes
  was characterized by correlations between total
  number of T-reg and NK and was associated with
  fall of CTL proliferative activity

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Acknowledgements
Evgenia V. Shmeleva Olga S. Kapitonova Irina P.
Balmasova Olga O. Znoiko Nikolay D. Yuschuk
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Thank you for your attention!