Normalization of immune activation in lymphoid tissue following highly active antiretroviral therapy

Homira Behbahani, Alan Landay, Bruce K. Patterson, Paul Jones, John Pottage, Michelle Agnoli, Jan Andersson, Anna Lena Spetz

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Although significant progress has been made in understanding immune reconstitution in peripheral blood following highly active antiretroviral therapy (HAART), less is known about immune changes in lymphoid tissue. Here, the expression of cytokine proteins (interferon gamma [IFN-γ], interleukin [IL]-2, IL-4, IL-10, IL-1α, and IL-1β) and surface antigens (CD4, CD8, CD1a, CD68) as well as cellular proviral HIV-1 DNA were determined in sequential tonsil biopsies before and at 4, 12, and 48 to 56 weeks posttherapy by quantitative in situ image analysis and fluorescent in situ 5'-nuclease assay (FISNA). Despite plasma virus suppression, a fraction of tonsil cells harbored pro-viral DNA for up to 1 year. A fourfold to eightfold increase in CD8+ T cells in tissue compared with seronegative controls and an increased frequency of CD1a+ dendritic cells prior to HAART reached control levels at week 56. The frequency of IFN-γ expressing cells was 10- to 15-fold higher than controls before therapy and was comparable with findings in seronegative controls by week 56. Elevated baseline expression of IL-1α and IL-1β was reduced by week 4 but IL-1α levels remained elevated in 1 of 3 patients at week 56. These findings suggest that with effective viral suppression the immune system in tissue may return to a more resting state.

Original languageEnglish (US)
Pages (from-to)150-156
Number of pages7
JournalJournal of Acquired Immune Deficiency Syndromes
Volume25
Issue number2
DOIs
StatePublished - Oct 1 2000
Externally publishedYes

Keywords

  • Cytokines
  • HAART
  • HIV
  • Lymphoid tissue
  • Pathogenesis
  • Viral load

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

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