Pohling, Julia and Zipperlen, Katrin and Hollett, Natasha A. and Gallant, Maureen E. and Grant, Michael D. (2010) Human immunodeficiency virus type I-specific CD8 + T cell subset abnormalities in chronic infection persist through effective antiretroviral therapy. BMC Infectious Diseases, 10 (129). pp. 1-10. ISSN 1471-2334
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Background: Effective highly active antiretroviral therapy (HAART) reduces human immunodeficiency virus (HIV) replication, restores CD4 +T lymphocyte counts and greatly reduces the incidence of opportunistic infections. While this demonstrates improved generalized immune function, rapid rebound to pre-treatment viral replication levels following treatment interruption indicates little improvement in immune control of HIV replication. The extent to which HAART can normalize HIV-specific CD8 +T cell function over time in individuals with chronic infection remains an important unresolved issue. In this study, we evaluated the magnitude, general specificity and character of HIV specific CD8 +T cell responses at four time points across 2-9 years in 2 groups of chronically infected individuals separated on the basis of either effective antiretroviral suppression or ongoing replication of HIV.Methods: Peripheral blood mononuclear cells (PBMC) were stimulated with overlapping 15mer peptides spanning HIV Gag, Pol, Env and Nef proteins. Cells producing interferon-γ (IFN-γ) or interleukin-2 (IL-2) were enumerated by ELISPOT and phenotyped by flow cytometry.Results and Conclusions: The magnitude of the HIV-specific CD8 +T cell response ranged from < .01 to approximately 1.0% of PBMC and was significantly greater in the group with detectable viral replication. Stronger responses reflected higher numbers of CD8 +CD45RA -effector memory cells producing IFN-γ, but not IL-2. Magnitude, general specificity and character of the HIV-specific CD8 +T cell response changed little over the study period. While antiretroviral suppression of HIV in chronic infection reduces HIV-specific CD8 +T cell response magnitude in the short term, it had no significant effect on response character over periods up to 9 years.
|Keywords:||RHesueamrch aartnicl eimmunodeficiency virus type I-specific CD8+ T cell subset abnormalities in chronic infection persist through effective antiretroviral therapy; antigen specificity; article; CD8+ T lymphocyte; cell stimulation; clinical article; controlled study; drug efficacy; enzyme linked immunospot assay; flow cytometry; human; human cell; Human immunodeficiency virus 1; Human immunodeficiency virus 1 infection; lymphocyte count; memory T lymphocyte; peripheral blood mononuclear cell; phenotype; sensitivity and specificity; T lymphocyte subpopulation; virus replication|
|Department(s):||Medicine, Faculty of|
|Date:||25 May 2010|
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