HCV-specific T-cell Responses (hcv-specific t-cell + response)

Distribution by Scientific Domains

Selected Abstracts

Immunosuppression for liver transplantation in HCV-infected patients: Mechanism-based principles

Bijan Eghtesad
We retrospectively analyzed 42 hepatitis C virus (HCV)-infected patients who underwent cadaveric liver transplantation under two strategies of immunosuppression: (1) daily tacrolimus (TAC) throughout and an initial cycle of high-dose prednisone (PRED) with subsequent gradual steroid weaning, or (2) intraoperative antithymocyte globulin (ATG) and daily TAC that was later space weaned. After 36 4 months, patient and graft survival in the first group was 18/19 (94.7%) with no examples of clinically serious HCV recurrence. In the second group, the three-year patient survival was 12/23 (52%), and graft survival was 9/23 (39%); accelerated recurrent hepatitis was the principal cause of the poor results. The data were interpreted in the context of a recently proposed immunologic paradigm that is equally applicable to transplantation and viral immunity. In the framework of this paradigm, the disparate hepatitis outcomes reflected different equilibria reached under the two immunosuppression regimens between the relative kinetics of viral distribution (systemically and in the liver) and the slowly recovering HCV-specific T-cell response. As a corollary, the aims of treatment of the HCV-infected liver recipients should be to predict, monitor, and equilibrate beneficial balances between virus distribution and the absence of an immunopathologic antiviral T-cell response. In this view, favorable equilibria were accomplished in the nonweaned group of patients but not in the weaned group. In conclusion, since the anti-HCV response is unleashed when immunosuppression is weaned, treatment protocols that minimize disease recurrence in HCV-infected allograft recipients must balance the desire to reduce immunosuppression or induce allotolerance with the need to prevent antiviral immunopathology. (Liver Transpl 2005;11:1343,1352.) [source]

Polyfunctional HCV-specific T-cell responses are associated with effective control of HCV replication

Donatella Ciuffreda
Abstract HCV infection has a severe course of disease in HIV/HCV co-infection and in liver transplant recipients. However, the mechanisms involved remain unclear. Here, we evaluated functional profiles of HCV-specific T-cell responses in 86 HCV mono-infected patients, 48 HIV/HCV co-infected patients and 42 liver transplant recipients. IFN-, and IL-2 production and ability of CD4 and CD8 T cells to proliferate were assessed after stimulation with HCV-derived peptides. We observed that HCV-specific T-cell responses were polyfunctional in HCV mono-infected patients, with presence of proliferating single IL-2-, dual IL-2/IFN-, and single IFN-,-producing CD4+ and dual IL-2/IFN-, and single IFN-,-producing CD8+ cells. In contrast, HCV-specific T-cell responses had an effector profile in HIV/HCV co-infected individuals and liver transplant recipients with absence of single IL-2-producing HCV-specific CD4+ and dual IL-2/IFN-,-producing CD8+ T cells. In addition, HCV-specific proliferation of CD4+ and CD8+ T cells was severely impaired in HIV/HCV co-infected patients and liver transplant recipients. Importantly, "only effector" T-cell responses were associated with significantly higher HCV viral load and more severe liver fibrosis scores. Therefore, the present results suggest that immune-based mechanisms may contribute to explain the accelerated course of HCV infection in conditions of HIV-1 co-infection and liver transplantation. [source]

Hepatitis C virus-specific T-cell immune responses in seronegative injection drug users

M. Zeremski
Summary., T-cell responses to hepatits C virus (HCV) antigens have been reported in high-risk HCV seronegative persons, suggesting that an effective cellular immune response might be able to clear infection without the development of antibodies. Such findings, however, could be explained by waning antibody or cross-reactivity to other antigens. To address these issues, we evaluated HCV-specific T-cell responses in 26 young (age 18,33 years) aviremic, seronegative injection drug users (IDUs) (median duration of injection, 6 years) by interferon-, enzyme-linked immunospot (ELISpot) assay using 429 overlapping HCV peptides pooled in 21 mixes. Seventeen aviremic, seropositive IDUs (spontaneous resolvers) and 15 healthy people were used as positive and negative controls, respectively. The percentage of patients with HCV-specific cellular immune responses was similar in seronegative and seropositive aviremic IDUs (46%vs 59%, P = 0.4), while these responses were not detected in any of the negative controls. Among the seronegative IDUs, six (23%) had intermediate to very strong responses to 10,20 peptide mixes and another six (23%) had moderately strong responses for two to six mixes. The 12 seronegative IDUs with HCV-specific T-cell responses had higher demographical and behavioural risk profiles than the 14 IDUs without T-cell responses (estimated risk of HCV infection, 0.47 vs 0.26, P < 0.01). In conclusion, HCV-specific T-cell responses are common among high-risk, seronegative IDUs. The responses are broad and are associated with risk factors for HCV exposure, suggesting that they reflect true exposure to HCV in seronegative persons. [source]

HCV-specific T-cell responses in injecting drug users: evidence for previous exposure to HCV and a role for CD4+ T cells focussing on nonstructural proteins in viral clearance

T. A. Ruys
Summary., In order to understand the parameters associated with resolved hepatitis C virus (HCV)-infection, we analysed the HCV-specific T-cell responses longitudinally in 13 injecting drug-users (IDUs) with a prospectively identified acute HCV infection. Seven IDUs cleared HCV and six IDUs remained chronically infected. T-cell responses were followed in the period needed to resolve and a comparable time span in chronic carriers. Ex vivo T-cell responses were measured using interferon-, Elispot assays after stimulation with overlapping peptide pools spanning the complete HCV genome. CD4+ memory- T-cell responses were determined after 12-day stimulation with HCV proteins. The maximum response was compared between individuals. The T-cell responses measured directly ex vivo were weak but significantly higher in resolvers compared to chronic carriers, whereas the CD4+ memory -T-cell response was not different between resolvers and chronic carriers. However, HCV Core protein was targeted more often in chronic carriers compared to individuals resolving HCV infection. CD4+ T-cell responses predominantly targeting nonstructural proteins were associated with resolved HCV infection. Interestingly, observation of memory-T-cell responses present before the documented HCV-seroconversion suggests that reinfections in IDUs occur often. The presence of these responses however, were not predictive for the outcome of infection. However, a transition of the HCV-specific CD4+ memory -T-cell response from targeting Core to targeting nonstructural proteins during onset of infection was associated with a favourable outcome. Therefore, the specificity of the CD4+ memory -T-cell responses measured after 12-day expansion seems most predictive of resolved infection. [source]