Abstract
BackgroundMHC-II restricted CD4+ T cells are dependent on antigen presenting cells (APC) for their activation. APC dysfunction in HIV-infected individuals could accelerate or exacerbate CD4+ T cell dysfunction and may contribute to increased levels of immunodeficiency seen in some patients regardless of their CD4+ T cell numbers. Here we test the hypothesis that APC from HIV-infected individuals have diminished antigen processing and presentation capacity.Methodology/Principal FindingsMonocytes (MN) were purified by immuno-magnetic bead isolation techniques from HLA-DR1.01+ or DR15.01+ HIV-infected and uninfected individuals. MN were analyzed for surface MHC-II expression and for antigen processing and presentation capacity after overnight incubation with soluble antigen or peptide and HLA-DR matched T cell hybridomas. Surface expression of HLA-DR was 20% reduced (p<0.03) on MN from HIV-infected individuals. In spite of this, there was no significant difference in antigen processing and presentation by MN from 14 HIV-infected donors (8 HLA-DR1.01+ and 6 HLA-DR15.01+) compared to 24 HIV-uninfected HLA-matched subjects.Conclusions/SignificanceWe demonstrated that MHC class II antigen processing and presentation is preserved in MN from HIV-infected individuals. This further supports the concept that this aspect of APC function does not further contribute to CD4+ T cell dysfunction in HIV disease.
Highlights
Activation of CD4+ T cells is dependent on presentation of antigen by MHC-II molecules on antigen presenting cells (APC)
We sought to determine the functional consequences of this HLA-DR reduction by measuring antigen presentation in these same MN
APC dysfunction could be a significant factor in immune dysfunction since both cell mediated and humoral immunity rely on APC function to activate their specific responses
Summary
Activation of CD4+ T cells is dependent on presentation of antigen by MHC-II molecules on APC. Two studies from Blauvelt et al measured antigen presentation in HIV-discordant identical twins [5,6]. Fidler et al used CD4+ T cell clones from uninfected subjects to measure antigen presentation by MN from HIV-infected individuals. They found a defect in antigen presentation that varied in magnitude depending on which T cell clone they tested [7]. These sets of studies using primary T cells to determine antigen presentation function demonstrate conflicting results. We test the hypothesis that APC from HIV-infected individuals have diminished antigen processing and presentation capacity
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