HEPATITIS

Diminished frequency of hepatitis C virus specific interferon secreting CD4+ T cells in human immunodeficiency virus/hepatitis C virus coinfected patients

G Harcourt¹, E Gomperts², S Donfield³, P Klenerman¹ the Hemophilia Growth and Development Study

¹ Nuffield Department of Medicine, University of Oxford, Peter Medawar Building for Pathogen Research, Oxford, UK
² Children’s Hospital Los Angeles, Los Angeles, California, USA
³ Rho, Chapel Hill, North Carolina, USA

Correspondence to:
Dr P Klenerman
Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, South Parks Road, Oxford OX1 3SY, UK; paul.klenerman{at}medawar.ox.ac.uk

Background: Human immunodeficiency virus/hepatitis C virus (HIV/HCV) coinfection is a common and complex clinical problem in which loss of immunological control of HCV occurs, with increased HCV viral load and more aggressive liver disease. Cellular immune responses, particularly secretion of interferon (IFN-) appear to be important in the control of HCV, and a detectable HCV specific CD4 response is associated with clearance of the virus. HCV specific CD8+ T cell responses, weak in chronic HCV infection, have been shown to be further impaired in HIV coinfection and this CD8+ T cell deficiency is related to the decline in CD4 T cell count.

Aims: To compare the CD4 T cell response to HCV in HIV/HCV coinfected and HCV monoinfected individuals and to determine the relationship of responses with declining CD4 count.

Patients: The study subjects were a cohort of 68 HCV monoinfected and 67 HCV/HIV coinfected haemophiliac children and adolescents (the Hemophilia Growth and Development Study) who were followed for a seven year period.

Methods: We analysed IFN- secreting CD4+ responses to HCV proteins and peptides and HIV p24 antigen using an ELISpot assay.

Results: We found a significant decrease in HCV specific responses among those who were HIV coinfected (10/67 v 36/68; p<0.0001) both in numbers of responders and frequency of specific cells. This did not appear to be closely related to CD4 count.

Conclusions: The reduction in HCV specific CD4 T cells in coinfection provide a cellular mechanism for the loss of control of HCV in coinfected individuals, even in those with relatively preserved CD4+ T cell counts and CD4+ T cell responses to HIV.

Abbreviations: HCV, hepatitis C virus; HIV, human immunodeficiency virus; IFN-, interferon ; EBV, Epstein-Barr virus; HAART, highly active antiretroviral therapy; PBMC, peripheral blood mononuclear cell

Keywords: hepatitis C virus; human immunodeficiency virus; CD4+ T cells; coinfection

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

Relevant Article

Digest

Robin Spiller
Gut 2006 55: 1373. [Extract] [Full Text] [PDF]

This article has been cited by other articles:

• Gonzalez, V. D., Falconer, K., Blom, K. G., Reichard, O., Morn, B., Laursen, A. L., Weis, N., Alaeus, A., Sandberg, J. K. (2009). High Levels of Chronic Immune Activation in the T-Cell Compartments of Patients Coinfected with Hepatitis C Virus and Human Immunodeficiency Virus Type 1 and on Highly Active Antiretroviral Therapy Are Reverted by Alpha Interferon and Ribavirin Treatment. J. Virol. 83: 11407-11411 [Abstract] [Full Text]  
• Rotman, Y., Liang, T. J. (2009). Coinfection with Hepatitis C Virus and Human Immunodeficiency Virus: Virological, Immunological, and Clinical Outcomes. J. Virol. 83: 7366-7374 [Full Text]  
• Chang, J. J., Sirivichayakul, S., Avihingsanon, A., Thompson, A. J. V., Revill, P., Iser, D., Slavin, J., Buranapraditkun, S., Marks, P., Matthews, G., Cooper, D. A., Kent, S. J., Cameron, P. U., Sasadeusz, J., Desmond, P., Locarnini, S., Dore, G. J., Ruxrungtham, K., Lewin, S. R. (2009). Impaired Quality of the Hepatitis B Virus (HBV)-Specific T-Cell Response in Human Immunodeficiency Virus Type 1-HBV Coinfection. J. Virol. 83: 7649-7658 [Abstract] [Full Text]  
• Radziewicz, H., Ibegbu, C. C., Hon, H., Osborn, M. K., Obideen, K., Wehbi, M., Freeman, G. J., Lennox, J. L., Workowski, K. A., Hanson, H. L., Grakoui, A. (2008). Impaired Hepatitis C Virus (HCV)-Specific Effector CD8+ T Cells Undergo Massive Apoptosis in the Peripheral Blood during Acute HCV Infection and in the Liver during the Chronic Phase of Infection. J. Virol. 82: 9808-9822 [Abstract] [Full Text]