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

Angélique Biancotto, Jean-Charles B. Grivel, Sarah J. Iglehart, Christophe Vanpouille, Andrea Lisco, Scott F. Sieg, Robert Debernardo, Kristen Garate, Benigno Rodriguez, Leonid B. Margolis, Michael M. Lederman

Research output: Contribution to journalArticle

154 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)4272-4279
Number of pages8
JournalBlood
Volume109
Issue number10
DOIs
Publication statusPublished - 15 May 2007
Externally publishedYes

Fingerprint

T-cells
HIV-1
Lymph Nodes
Chemical activation
Cytokines
HIV Infections
T-Lymphocytes
Interleukin-15
Death Domain Receptors
Lymphocytes
Immune system
CD95 Antigens
Cell death
Lymphocyte Subsets
Interleukin-2
Lymphoid Tissue
Dendritic Cells
Immune System
Tissue
Cell Death

ASJC Scopus subject areas

  • Immunology
  • Biochemistry
  • Hematology
  • Cell Biology

Cite this

Biancotto, A., Grivel, J-C. B., Iglehart, S. J., Vanpouille, C., Lisco, A., Sieg, S. F., ... Lederman, M. M. (2007). Abnormal activation and cytokine spectra in lymph nodes of people chronically infected with HIV-1. Blood, 109(10), 4272-4279. https://doi.org/10.1182/blood-2006-11-055764

Abnormal activation and cytokine spectra in lymph nodes of people chronically infected with HIV-1. / Biancotto, Angélique; Grivel, Jean-Charles B.; Iglehart, Sarah J.; Vanpouille, Christophe; Lisco, Andrea; Sieg, Scott F.; Debernardo, Robert; Garate, Kristen; Rodriguez, Benigno; Margolis, Leonid B.; Lederman, Michael M.

In: Blood, Vol. 109, No. 10, 15.05.2007, p. 4272-4279.

Research output: Contribution to journalArticle

Biancotto, A, Grivel, J-CB, Iglehart, SJ, Vanpouille, C, Lisco, A, Sieg, SF, Debernardo, R, Garate, K, Rodriguez, B, Margolis, LB & Lederman, MM 2007, 'Abnormal activation and cytokine spectra in lymph nodes of people chronically infected with HIV-1', Blood, vol. 109, no. 10, pp. 4272-4279. https://doi.org/10.1182/blood-2006-11-055764
Biancotto, Angélique ; Grivel, Jean-Charles B. ; Iglehart, Sarah J. ; Vanpouille, Christophe ; Lisco, Andrea ; Sieg, Scott F. ; Debernardo, Robert ; Garate, Kristen ; Rodriguez, Benigno ; Margolis, Leonid B. ; Lederman, Michael M. / Abnormal activation and cytokine spectra in lymph nodes of people chronically infected with HIV-1. In: Blood. 2007 ; Vol. 109, No. 10. pp. 4272-4279.
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