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Natural Killer Cell Subsets
Monday, 1:30 - 3:30 pm
Background: CD81 is a trans-membrane protein and was shown to bind hepatitis C virus envelope 2 protein. CD81 cross-linking enhances anti-CD3 activation of T cells in regard to IFN-g production and is required for maintainance of a T–helper response necessary to preserve strong CTL function. Cross-linking of CD81 blocks NK cell activation, cytokine production, cytotoxic granule release, and proliferation.
Methods: Aim of the study was to analyze CD81 cell surface and mRNA expression on CD4+ and CD8+ lymphocytes in healthy controls, HIV-1, HCV, and dually infected subjects. CD81 expression on NK cells was also evaluated in 51 HIV-1+ patients and 15 HC. CD81 cell surface expression was measured by means of flow cytometry; we measured the mean fluorescence (MFI) channel of CD81 positive peak on gated CD4+, CD8+, and CD16+ cells. mRNA quantitation was performed with relative quantitative PCR using TaqMan on CD4 and CD8 T cells sorted with magnetic beads. Statistical analysis was performed with Student’s t-Test.
Results: MFI for CD81 on CD4 lymphocytes was significantly lower in HIV+HCV- patients (median value 29,152) and in HIV+HCV+ patients (median value 27,151) compared both with HIV-HCV+ patients (median value 37,683) and with HIV-HCV- healthy controls (median value 39,568, 5) (p <0.05), therefore stratifying the studied population according to HIV infection MFI for CD81 was significantly lower on CD4 cells from HIV+ patients than in HIV- patients (p = 0.007). No difference in MFI for CD81 was observed on CD8 T cells among the four groups. NK cells from HIV-1 infected individuals displayed an increased expression of surface CD81 compared to HC even though the difference did not reach statistical significance. CD81 mRNA in CD4+ cells was significantly higher in HIV+ patients compared to HIV- subjects (p = 0.002).
Conclusions: Our results show that HIV-1 infection down-regulates CD81 on CD4+ T cells and upregulates CD81 on NK cells. As CD81 cross-linking mediates completely different signals in NK cells vs T cells, modulation of CD81 by HIV-1 can alter both innate immunity through inhibition of IFN-g production by NK cells.and acquired immunity because of a reduction of IFN-g production and weakness of CTL specific response and therefore favor HIV-1 disease progression and cause susceptibility to different infectious agents and to Epstein-Barr virus-induced oncogenesis. Up-regulation of CD81 mRNA on CD4+ cells indicates that down-regulation of CD81 protein occurs at the posttranscriptional/translational level.
Keywords: CD81; NK; T lymphocytes