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 language | English |
|---|---|
| Pages (from-to) | 2339-2350 |
| Number of pages | 12 |
| Journal | Journal of Experimental Medicine |
| Volume | 203 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - 2006 |
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ASJC Scopus subject areas
- Immunology
Cite this
Characterization of the defective interaction between a subset of natural killer cells and dendritic cells in HIV-1 infection. / Mavilio, Domenico; Lombardo, Gabriella; Kinter, Audrey; Fogli, Manuela; La Sala, Andrea; Ortolano, Saida; Farschi, Annahita; Follmann, Dean; Gregg, Roby; Kovacs, Colin; Marcenaro, Emanuela; Pende, Daniela; Moretta, Alessandro; Fauci, Anthony S.
In: Journal of Experimental Medicine, Vol. 203, No. 10, 2006, p. 2339-2350.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Characterization of the defective interaction between a subset of natural killer cells and dendritic cells in HIV-1 infection
AU - Mavilio, Domenico
AU - Lombardo, Gabriella
AU - Kinter, Audrey
AU - Fogli, Manuela
AU - La Sala, Andrea
AU - Ortolano, Saida
AU - Farschi, Annahita
AU - Follmann, Dean
AU - Gregg, Roby
AU - Kovacs, Colin
AU - Marcenaro, Emanuela
AU - Pende, Daniela
AU - Moretta, Alessandro
AU - Fauci, Anthony S.
PY - 2006
Y1 - 2006
N2 - 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.
AB - 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.
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U2 - 10.1084/jem.20060894
DO - 10.1084/jem.20060894
M3 - Article
VL - 203
SP - 2339
EP - 2350
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
SN - 0022-1007
IS - 10
ER -