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Even with sustained antiretroviral therapy, resting CD4 T cells remain a persistent reservoir of HIV infection, representing a critical barrier to curing HIV. Here, we demonstrate that CD8 T cells recognize infected, non-activated CD4 T cells in the absence of de novo protein production, as measured by immune synapse formation, degranulation, cytokine production, and killing of infected cells. Immune recognition is induced by HLA-I presentation of peptides derived from incoming viral particles, and recognition occurred either following cell-free virus infection or following cell-to-cell spread. CD8 T cells from HIV controllers mediate more effective immune recognition than CD8 T cells from progressors. These results indicate that non-activated HIV-infected CD4 T cells can be targeted by CD8 T cells directly after HIV entry, before reverse transcription, and thus before the establishment of latency, and suggest a mechanism whereby the immune response may reduce the size of the HIV reservoir.
This article was published in the following journal.
Name: Cell reports
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Cell adhesion molecule expressed on activated leukocytes, fibroblasts, and neurons. It is a ligand for CD6. ALCAM-CD6 interactions may play a role in the binding of T and B cells to activated leukocytes.
A 44-kD stimulatory receptor found on activated NATURAL KILLER CELLS. It has specificity for VIRAL HEMAGGLUTININS that are expressed on infected cells.
A 46-kD stimulatory receptor found on resting and activated NATURAL KILLER CELLS. It has specificity for VIRAL HEMAGGLUTININS that are expressed on infected cells.
Bone marrow-derived lymphocytes that possess cytotoxic properties, classically directed against transformed and virus-infected cells. Unlike T CELLS; and B CELLS; NK CELLS are not antigen specific. The cytotoxicity of natural killer cells is determined by the collective signaling of an array of inhibitory and stimulatory CELL SURFACE RECEPTORS. A subset of T-LYMPHOCYTES referred to as NATURAL KILLER T CELLS shares some of the properties of this cell type.
A heterogeneous group of immunocompetent cells that mediate the cellular immune response by processing and presenting antigens to the T-cells. Traditional antigen-presenting cells include MACROPHAGES; DENDRITIC CELLS; LANGERHANS CELLS; and B-LYMPHOCYTES. FOLLICULAR DENDRITIC CELLS are not traditional antigen-presenting cells, but because they hold antigen on their cell surface in the form of IMMUNE COMPLEXES for B-cell recognition they are considered so by some authors.