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Cell-Associated HIV Cross-Presentation by Plasmacytoid Dendritic Cells Is Potentiated by Noncognate CD8 + T Cell Preactivation

Abstract : Human plasmacytoid dendritic cells (pDC) can cross-present antigens from apoptotic HIV-infected cells or tumor cells to CD8+ T cells. As pDC respond to HIV virions by maturing and secreting cytokines, we wondered whether this affect cross-presentation from HIV-infected cells. We incubated purified blood DC with apoptotic HIV-infected H9 cells, then explored the activation process of HIV-specific cloned CD8+ T cells, in the presence of saquinavir We studied IFN- secretion by HIV-specific T cells, which is known to be tightly regulated by engagement of the T cell receptor. We found that this secretion was stimulated by pDC and cDC1 more than by cDC2, and was strictly MHC-Class I-restricted. Surprisingly, intracellular production of IFN-γ was only partly MHC-I restricted for pDC, indicating a non-cognate CD8+ T cell activation. Plasmacytoid DC, but not cDC, matured and secreted IFN- in the presence of apoptotic H9HIV cells. A cocktail of IFN-, IFN- and TNF- induced intracellular production of IFN-γ but not Granzyme-B, mimicking the non-cognate mechanism. Neutralization of type I IFN signaling blocked non-cognate intracellular production of IFN-γ. Moreover, cognate stimulation was required to induce IFN-γ secretion in addition to the cytokine cocktail. Thus, IFN-γ secretion is tightly regulated by engagement of the TCR as expected, but in the context of virus-infected cells, pDC can trigger intracellular IFN-γ accumulation in CD8+ T cells, potentiating IFN-γ secretion once CD8+ T cells make cognate interactions. These findings may help manipulate type I IFN signaling to enhance specifically antigen-specific CD8+ T cell activation against chronic infections or tumors.
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https://hal-cnrs.archives-ouvertes.fr/hal-03453498
Contributor : Anne Hosmalin Connect in order to contact the contributor
Submitted on : Monday, November 29, 2021 - 10:33:29 PM
Last modification on : Thursday, April 7, 2022 - 1:58:21 PM

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Stéphane Isnard, Etienne Hatton, Marco Iannetta, Jean-Baptiste Guillerme, Anne Hosmalin. Cell-Associated HIV Cross-Presentation by Plasmacytoid Dendritic Cells Is Potentiated by Noncognate CD8 + T Cell Preactivation. Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2021, 207 (1), pp.15-22. ⟨10.4049/jimmunol.2000392⟩. ⟨hal-03453498⟩

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