NK cell activation by dendritic cells is dependent on LFA-1-mediated induction of calcium-calmodulin kinase II

Inhibition by HIV-1 Tat C-terminal domain

A. Poggi, R. Carosio, G. M. Spaggiari, C. Fortis, G. Tambussi, G. Dell'Antonio, E. C. Cin, A. Rubartelli, M. R. Zocchi

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Abstract

In this study, we show that binding to autologous dendritic cells (DC) induces a calcium influx in NK cells, followed by activation of the calcium-calmodulin kinase II (CAMKII), release of perforin and granzymes, and IFN-y secretion. CAMKII is induced via LFA-1: indeed, oligomerization of LFA-1 leads to CAMKII induction in NK cells. Moreover, release of lytic enzymes and cytotoxic activity is strongly reduced by masking LFA-1 or by adding CAMKII inhibitors such as KN62 and KN93, at variance with the inactive compound KN92. NK cell-mediated lysis of DC and IFN-γ release by NK cells upon NK/DC contact are inhibited by exogenous HIV-1 Tat: the protein blocks calcium influx and impairs CAMKII activation elicited via LFA-1 in NK cells, eventually inhibiting degranulation. Experiments performed with synthetic, overlapping Tat-derived peptides showed that the C-terminal domain of the protein is responsible for inhibition. Finally, both KN62 and Tat reduced the extension of NK/DC contacts, possibly affecting NK cell granule polarization toward the target. These data provide evidence that exogenous Tat inhibits NK cell activation occurring upon contact with DC: this mechanism might contribute to the impairment of natural immunity in HIV-1 infection.

Original languageEnglish
Pages (from-to)95-101
Number of pages7
JournalJournal of Immunology
Volume168
Issue number1
Publication statusPublished - Jan 1 2002

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Lymphocyte Function-Associated Antigen-1
Calcium-Calmodulin-Dependent Protein Kinases
Natural Killer Cells
Dendritic Cells
HIV-1
Calcium
Human Immunodeficiency Virus tat Gene Products
Granzymes
Perforin
Innate Immunity
HIV Infections

ASJC Scopus subject areas

  • Immunology

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NK cell activation by dendritic cells is dependent on LFA-1-mediated induction of calcium-calmodulin kinase II : Inhibition by HIV-1 Tat C-terminal domain. / Poggi, A.; Carosio, R.; Spaggiari, G. M.; Fortis, C.; Tambussi, G.; Dell'Antonio, G.; Cin, E. C.; Rubartelli, A.; Zocchi, M. R.

In: Journal of Immunology, Vol. 168, No. 1, 01.01.2002, p. 95-101.

Research output: Contribution to journalArticle

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