Abnormal activation and cytokine spectra in lymph nodes of people chronically infected with HIV-1.

Full Abstract

There is growing recognition that HIV-1 infection leads to an activation of the immune system that includes perturbations of cytokine expression, redistribution of lymphocyte subpopulations, cell dysfunction, and cell death. Here, we explored the relationships between HIV-1 infection and immune activation in chronically HIV-1-infected human lymph nodes. In addition to CD4 T-cell depletion, we found increased effector T-cell frequencies associated with profound up-regulation of an activation marker CD38 in naive, central memory, and effector CD4(+) and CD8(+) T cells. Likewise, Fas death receptor (CD95) was more frequently detectable on T cells from HIV-1 nodes. Dendritic cell (DC) depletion was dramatic, with plasmacytoid DCs (PDCs) 40-fold and myeloid DCs (MDCs) 20-fold less frequent in HIV(+) nodes than in control nodes. Cytokine dysregulation was evident, with IL-2 and IL-15 as much as 2 or 3 logs greater in infected nodes than in control nodes. Thus, activated effector cells are inappropriately attracted and/or retained in lymphoid tissue in chronic HIV-1 infection. High-level cytokine expression in turn activates and retains more cells at these sites, leading to lymphadenopathy and massive bystander activation that characterizes HIV-1 infection. Strategies targeting these activation pathways may lead to new therapies.

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Author information

Author/s: Biancotto, Angélique (A); Grivel, Jean-Charles (JC); Iglehart, Sarah J (SJ); Vanpouille, Christophe (C); Lisco, Andrea (A); Sieg, Scott F (SF); Debernardo, Robert (R); Garate, Kristen (K); Rodriguez, Benigno (B); Margolis, Leonid B (LB); Lederman, Michael M (MM);

Affiliation: Laboratory of Molecular and Cellular Biophysics, National Institute of Child Health and Human Development, Bethesda, MD 20892, USA.

Grants: AI 36219 (Agency:NIAID NIH HHS)

Journal and publication information

Publication Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural

Journal: Blood (Blood), published in United States. (Language: eng)

Reference: 2007-May; vol 109 (issue 10) : pp 4272-9

Dates: Created 2007/05/07; Completed 2007/07/12; Revised 2008/11/20;

PMID: 17289812, status: MEDLINE (last retrieval date: 12/26/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Adult
Aged
Antigens, CD38 - genetics; metabolism
CD4-Positive T-Lymphocytes - metabolism
Case-Control Studies
Chronic Disease
Cytokines - metabolism
Female

Female
Gene Expression Regulation
HIV Infections - metabolism
HIV-1
Humans
Lymph Nodes - metabolism
Male
Middle Aged

Associated Chemicals: Cytokines (0) ; Antigens, CD38 (EC 3.2.2.5)

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