Distribution of Bulk and HIV-specific CD8+ T cell Memory Phenotypes during Acute/Early HIV Infection is Related to Reduced Antiviral Activity.

YANINA GHIGLIONE; JULIANA FALIVENE; MARÍA JULIA RUIZ; NATALIA LAUFER; MARÍA EUGENIA SOCIAS; PEDRO CAHN; OMAR SUED; MARÍA MAGDALENA GHERARDI; HORACIO SALOMÓN; GABRIELA TURK

Ciudad del Cabo

Conferencia; HIV-R4P. Research for Prevention; 2014

Global HIV Vaccine Enterprise

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. 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. 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). 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.