학술논문
Differential expression of IFN-α and TRAIL/DR5 in lymphoid tissue of progressor versus nonprogressor HIV-1-infected patients
Document Type
Author abstract
Author
Source
Proceedings of the National Academy of Sciences of the United States. May 2, 2006, Vol. 103 Issue 18, p7000, 6 p.
Subject
Language
English
ISSN
0027-8424
Abstract
Loss of CD4+ T cells, the hallmark of HIV pathogenesis, was suggested to be partly due to apoptosis. We recently reported that IFN-α produced by HIV-1-activated plasmacytoid dendritic cells (pDCs) contributes to CD4+ T cell apoptosis by the TNF-related apoptosis-inducing ligand (TRAIL)/death receptor (DR)5 pathway. Here, we show that HIV-l-induced intracellular expression of IFN-α in pDCs is coupled to increased expression of IFN regulatory factor 7 and MyD88 by pDCs in vivo and in vitro. Expression of IFN-α was increased in lymphoid tonsillar tissue (LT) of patients with progressive ([HIV.sub.prog]) compared with nonprogressive ([HIV.sub.NP]) HIV-1 disease and to uninfected controls. LT from [HIV.sub.prog] exhibited higher TRAIL and DR5 mRNA levels than LT from [HIV.sub.NP] or controls. TRAIL mRNA levels in LT correlated with plasma viral load. We show that HIV-1 induces IFN-α and the TRAIL/DR5 apoptotic pathway in LT, suggesting a role for these cytokines in HIV-1 immunopathogenesis. pDC | IRF-7 | MyD88 | AT-2 HIV-1