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. 2011 Mar 15;203(6):847-53.
doi: 10.1093/infdis/jiq121.

Loss of virus-specific T-cell responses in HCV exposed uninfected injection drug users with drug rehabilitation

Prem H Thurairajah  1 , Doha Hegazy, Andrew Demaine, Edward R Kaminski, Matthew E Cramp
Affiliations

Loss of virus-specific T-cell responses in HCV exposed uninfected injection drug users with drug rehabilitation

Prem H Thurairajah et al. J Infect Dis. .

Abstract

Introduction: Hepatitis C virus (HCV)-specific T lymphocyte responses have been demonstrated in peripheral blood from injection drug users (IDUs) persistently HCV antibody and RNA negative despite high-risk behavior. We have termed these apparently HCV resistant cases "Exposed Uninfecteds" (EUs), and have studied the evolution of T-cell responses to determine if they are protective in nature.

Methods: Twenty-one EU cases were studied using a questionnaire to ascertain injecting behavior details. Peripheral blood mononuclear cells were isolated from whole blood and an interferon-gamma (IFN-γ) enzyme-linked immunosorbent spot (ELISPOT) assay used to detect T-cell responses to a panel of HCV proteins. EU cases were subdivided by injecting drug patterns into (1) cases in rehabilitation who stopped injecting, (2) prisoners (infrequent/noninjectors), and (3) cases who continued to inject.

Results: EUs continuing to inject had significantly stronger (P < .01) and more frequent (P < .05) HCV-specific IFN-γ ELISPOT responses than controls or noninjecting EUs. EUs in rehabilitation lost their T-cell responses during follow-up, while those continuing to inject maintained them.

Conclusions: HCV-specific T-cell responses in EU cases wane within months of cessation of injection drug use. Maintenance of these T-cell responses appears to be dependent on continuing HCV exposure through injection drug use.

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Figures

Figure 1.
Figure 1.
Breakdown of the total number of repeated tests and the proportions of positive IFN-γ assays among the 3 subsets. Those EUs who continued to inject or were in prison had a significantly higher proportion of ELISPOT positive assays to HCV antigens than EUs in rehabilitation or the controls (*P < .05). NOTE. IFN-γ: interferon gamma; EUs: exposed uninfecteds; ELISPOT: Enzyme linked immunosorbent spot; HCV: hepatitis C virus; DU: drug user.
Figure 2.
Figure 2.
(A) Longitudinal T-cell responses in controls. (B) Longitudinal T-cell responses in EUs in rehabilitation. (C) Longitudinal T-cell responses in EUs in prisons. (D) Longitudinal T-cell responses in EUs who continued to inject. NOTE. EUs: exposed uninfecteds; SFU: spot-forming unit.
Figure 3.
Figure 3.
Proportion of IFN-γ ELISPOT positive assays on repeat testing. NOTE. IFN-γ: interferon gamma; ELISPOT: Enzyme linked immunosorbent spot; DU: drug user.
Figure 4.
Figure 4.
Frequency of ELISPOT positive responses in a time dependent manner. The frequency of positive responses decrease with time since last injection, and significantly less frequent after 12 months. NOTE. ELISPOT: Enzyme linked immunosorbent spot.
Figure 5.
Figure 5.
Sum of IFN-γ ELISPOT responses to all 4 HCV antigens among the 3 EU groups and controls at all time points. EU cases who continued to inject had a significantly stronger response to HCV antigens than the other groups (**P < .01). NOTE. IFN-γ: interferon gamma; ELISPOT: Enzyme linked immunosorbent spot; HCV: hepatitis C virus; EU: exposed uninfected.
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