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Clinical and Developmental Immunology
Volume 13, Issue 2-4, Pages 369-372

HIV-1 Tat Triggers TGF-β Production and NK Cell Apoptosis that is Prevented by Pertussis Toxin B

1Laboratory of Experimental Oncology D, National Institute for Cancer Research, Genoa, Italy
2Laboratory of Tumor Immunology, Scientific Institute San Raffaele, Milan, Italy

Copyright © 2006 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Herein, we show that PTX-B and its non-toxic mutant PT9K/129G inhibit transcription and secretion of TGF-β elicited by HIV-1 Tat in NK cells. Moreover, Tat strongly activates the cJun component of the multimolecular complex AP-1, while TGF-β triggers cFos and cJun. Treatment of NK cells In turn,with PTX-B or PT9K/129G inhibits Tat and TGF-β-induced activation of AP-1. TGF-β enhances starvation-induced NK cell apoptosis, reduces the transcription of the antiapoptotic protein Bcl-2 and inhibits Akt phosphorylation induced by oligomerization of the triggering NK cell receptor NKG2D. All these TGF-β-mediated effects are prevented by PTX-B or PT9K/129G, through a PI-3K-dependent mechanism. Finally, PTX-B and PT9K/129G upregulate Bcl-xL, the isoform of Bcl-x that protects cells from starvation-induced apoptosis. Of note, in NK cells from patients with HIV-1 infection, mRNA expression of Bcl-2 and Bcl-xL was consistently lower than that of healthy donors; interestingly, TGF-β and Tat were detected in the sera of these patients. These data suggest that Tat-induced TGF-β production and the consequent NK cell failure, possibly occurring during early HIV-1 infection, may be regulated by PTX-B and PT9K/129G.