Profound loss of HCV-specific interferon-gamma secreting CD4+ T cells in HIV/HCV co-infected patients

Gillian Harcourt ¹, Ed Gomperts ², Sharyne Donfield ³ and Paul Klenerman ^1*

¹ University of Oxford, United Kingdom
² Children's Hospital, Los Angeles, United States
³ Rho, United States

^* To whom correspondence should be addressed. E-mail: paul.klenerman{at}ndm.ox.ac.uk.

Accepted 18 January 2006

Abstract

Background: HIV/HCV co-infection 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 IFN-gamma, appear to be important in 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 co-infection 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 co-infected and HCV mono-infected individuals and to determine the relationship of responses with declining CD4 count.

Patients: The study subjects were a cohort of 68 HCV mono-infected and 67 HCV/HIV co-infected haemophiliac children and adolescents (HGDS) who were followed for a seven year period.

Methods: We analysed IFN-gamma 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 co-infected (10/67 vs 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 co-infection provides a cellular mechanism for the loss of control of HCV in co-infected individuals, even in those with relatively preserved CD4+ T cell counts. The HCV-specific CD4 T cell loss appears to occur prior to the loss of HIV-specific CD4 T cells.

Keywords: CD4+ T cell, HCV, HIV

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