Proliferative Capacity of Epitope-Specific CD8 T-Cell Responses Is Inversely Related to Viral Load in Chronic Human Immunodeficiency Virus Type 1 Infection

Nuffield Department of Medicine, The Peter Medawar Building for Pathogen Research, South Parks Road, Oxford OX1 3SY, United Kingdom.
Journal of Virology (Impact Factor: 4.44). 02/2007; 81(1):434-8. DOI: 10.1128/JVI.01754-06
Source: PubMed


The relationship between the function of human immunodeficiency virus (HIV)-specific CD8 T-cell responses and viral load has not been defined. In this study, we used a panel of major histocompatibility complex class I tetramers to examine responses to frequently targeted CD8 T-cell epitopes in a large cohort of antiretroviral-therapy-naïve HIV type 1 clade C virus-infected persons in KwaZulu Natal, South Africa. In terms of effector functions of proliferation, cytokine production, and degranulation, only proliferation showed a significant correlation with viral load. This robust inverse relationship provides an important functional correlate of viral control relevant to both vaccine design and evaluation.

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    • "Antigen presentation and the relative amount of antigen presented through MHC class I play critical role in the process of T cell exhaustion [24] [25]. Whether high viral load through continuing replication of virus within the cells is sufficient to induce T cell exhaustion or additional mechanisms such as impairment of CD4 and NK cell activities are needed is still unclear [26]. Apart from LCMV, T cell exhaustion is also observed for many different chronic viruses including hepatitis C virus, hepatitis B Virus, HIV, and HTLV, etc. [27] [28]. "
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    • "Upon antigenic stimulation, differentiation of naïve CD8+ T cells, which eventually gives rise to the different compartments of T-cell memory subsets, has a substantial effect on the CD8+ T cell pool (Lanzavecchia and Sallusto, 2002). Impairment of this might contribute to the dysfunctional, ineffective anti-HIV-1 response (Wherry and Ahmed, 2004), unsettling the proliferative capacity of epitope-specific CD8 T cells that are inversely related to the plasma HIV-1 RNA load (Day et al., 2007). In addition, it has been shown that removal of antigen due to either initiation of cART or development of epitope escape mutations, results in diminished HIV-1-specific CD8 T-cell response over time (Janbazian et al., 2012). "
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    • "While many cell surface markers, activation profiles, and functional parameters of both ex vivo HIV-specific CD8+ and CD4+ T cells have been shown to correlate with control of viremia [8], [30], [31], [32], [33] few, if any, can potentially mediate direct control of HIV replication through the lysis of infected cells [34]. Our lab has shown that Tim-3 expressing CD8+ T cells are dysfunctional in terms of polyfunctionality, proliferative ability, cytokine release and inhibitory receptor expression [15]. "
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