Distribution of Bulk and HIV-specific CD8 + T Cell Memory Phenotypes during Acute/Early HIV Infection Is Related to Reduced Antiviral Activity
Date
2014
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Abstract
Background: Memory CD8+ T-cells are important components of protective immunity. Understanding their development during primary HIV infection (PHI) may contribute to optimal vaccine design.
Aim: To analyze the distribution of memory subsets during PHI and their correlation with functionality and clinical parameters.
Methods: 19 samples from acutely infected subjects were obtained at baseline and 12 months post-infection (mpi). Phenotypic (CD45RO, CCR7, PD-1) and functional markers (cytokines) were used to identify bulk and HIV-specific CD8+ memory populations. CD8 virus inhibitory assay (VIA) was performed. Data was compared intra-group and correlated to clinical parameters, PD-1 analysis and CD8 antiviral activity, using non-parametric statistics.
Results: Bulk and HIV-specific CD8+ profile was terminal effectors (TE)>naïve>effector memory (TEM)>central memory. Spearman's correlation showed that baseline CD8+ VIA inversely correlated with the concurrent proportion of HIV-specific CD8+ TEM cells (r=-0.593, p=0.009) and directly correlated with the proportion of HIV-specific CD8+ TE cells (r=0.718, p=0.0008). Identical correlations were observed between baseline CD8+ T cell phenotype and CD8+ VIA at 12 mpi. Also, percentage of PD-1high CD8+ T cells negatively correlated with bulk and HIV-specific CD8+ TEM cells (r=−0.501, p=0.034 and r=−0.668, p=0.004, respectively). Conversely, positive correlations were observed with the proportion of bulk and HIV-specific CD8+ TE cells (r=-0.510, p=0.0308 and r=−0.564, p=0.022, respectively).
Conclusions: A higher proportion of fully differentiated HIV-specific cells are related to the magnitude of CD8+ antiviral activity (rapidly able to exert effector functions) and to a higher PD-1 expression (related to T cell differentiation stage and activation status). This is the first report were a relation between CD8+ T cell memory differentiation hierarchy and antiviral function is reported during acute infection, providing information potentially useful for vaccine design.
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Keywords
CD8+ T cells, HIV-specific memory, Antiviral activity
Citation
Ghiglione, Y., Falivene, J., Ruiz, M. J., Laufer, N., Socias, M. E., Cahn, P., ... & Turk, G. (2014). Distribution of bulk and HIV-specific CD8+ T cell memory phenotypes during acute/early HIV infection is related to reduced antiviral activity. AIDS Research and Human Retroviruses, 30(S1), A179-A179.