HIV-activated Human Plasmacytoid DCs Induce Tregs Through an Indoleamine 2,3-dioxygenase-dependent Mechanism

Overview

Journal J Clin Invest

Specialty General Medicine

Date 2008 Sep 9

PMID 18776940

Citations 119

Authors

Olivier Manches

David Munn

Anahita Fallahi

Jeffrey Lifson

Laurence Chaperot

Joel Plumas

Nina Bhardwaj

Affiliations

Soon will be listed here.

Abstract

Plasmacytoid DCs (pDCs) have been implicated as crucial cells in antiviral immune responses. On recognizing HIV, they become activated, secreting large amounts of IFN-alpha and inflammatory cytokines, thereby potentiating innate and adaptive antiviral immune responses. Here, we have shown that HIV-stimulated human pDCs can also induce the differentiation of naive CD4+ T cells into Tregs with suppressive function. This differentiation was independent of pDC production of IFN-alpha and primarily dependent on pDC expression of indoleamine 2,3-dioxygenase, which was induced through the TLR/MyD88 pathway, following binding of HIV to CD4 and triggering of TLR7 by HIV genomic RNA. Functionally, the Tregs induced by pDCs were shown to inhibit the maturation of bystander conventional DCs. This study therefore reveals what we believe to be a novel mechanism by which pDC may regulate and potentially limit anti-HIV immune responses.

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