Characterization of the defective interaction between a subset of natural killer cells and dendritic cells in HIV-1 infection

Domenico Mavilio, Gabriella Lombardo, Audrey Kinter, Manuela Fogli, Andrea La Sala, Saida Ortolano, Annahita Farschi, Dean Follmann, Roby Gregg, Colin Kovacs, Emanuela Marcenaro, Daniela Pende, Alessandro Moretta, Anthony S. Fauci

Research output: Contribution to journalArticlepeer-review

Abstract

In this study, we demonstrate that the in vitro interactions between a CD56neg/CD16pos (CD56neg) subset of natural killer (NK) cells and autologous dendritic cells (DCs) from HIV-1-infected viremic but not aviremic individuals are markedly impaired and likely interfere with the development of an effective immune response. Among the defective interactions are abnormalities in the process of reciprocal NK-DC activation and maturation as well as a defect in the NK cell-mediated editing or elimination of immature DCs (iDCs). Notably, the lysis of mature DCs (mDCs) by autologous NK cells was highly impaired even after the complete masking of major histocompatibility complex I molecules, suggesting that the defective elimination of autologous iDCs is at the level of activating NK cell receptors. In this regard, the markedly impaired expression/secretion and function of NKp30 and TNF-related apoptosis-inducing ligand, particularly among the CD56 neg NK cell subset, largely accounts for the highly defective NK cell-mediated lysis of autologous iDCs. Moreover, mDCs generated from HIV-1 viremic but not aviremic patients are substantially impaired in their ability to secrete interleukin (IL)-10 and -12 and to prime the proliferation of neighboring autologous NK cells, which, in turn, fail to secrete adequate amounts of interferon-γ.

Original languageEnglish
Pages (from-to)2339-2350
Number of pages12
JournalJournal of Experimental Medicine
Volume203
Issue number10
DOIs
Publication statusPublished - 2006

ASJC Scopus subject areas

  • Immunology

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