HIV-1 shedding from the female genital tract is associated with increased Th1 cytokines/chemokines that maintain tissue homeostasis and proportions of CD8+FOXP3+ T cells

Marta E. Bull*, Jillian Legard, Kenneth Tapia, Bess Sorensen, Susan E. Cohn, Rochelle Garcia, Sarah E. Holte, Robert W. Coombs, Jane E. Hitti

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Background: HIV-1 shedding from the female genital tract is associated with increased sexual and perinatal transmission and has been broadly evaluated in cross-sectional studies. However, few longitudinal studies have evaluated how the immune microenvironment effects shedding. Methods: Thirty-nine HIV-1-infected women had blood, cervicovaginal lavage, and biopsies of the uterine cervix taken quarterly for up to 5 years. Cytokines/chemokines were quantified by Luminex assay in cervicovaginal lavage, and cellular phenotypes were characterized using immunohistochemistry in cervical biopsies. Comparisons of cytokine/chemokine concentrations and the percent of tissue staining positive for T cells were compared using generalized estimating equations between non-shedding and shedding visits across all women and within a subgroup of women who intermittently shed HIV-1. Results: Genital HIV-1 shedding was more common when plasma HIV-1 was detected. Cytokines associated with cell growth (interleukin-7), Th1 cells/inflammation (interleukin-12p70), and fractalkine were significantly increased at shedding visits compared with non-shedding visits within intermittent shedders and across all subjects. Within intermittent shedders and across all subjects, FOXP3+ T cells were significantly decreased at shedding visits. However, there were significant increases in CD8+ cells and proportions of CD8+FOXP3+ T cells associated with HIV-1 shedding. Conclusions: Within intermittent HIV-1 shedders, decreases in FOXP3+ T cells at the shedding visit suggests that local HIV-1 replication leads to CD4 T-cell depletion, with increases in the proportion of CD8+FOXP3+ cells. HIV-1-infected cell loss may promote a cytokine milieu that maintains cellular homeostasis and increases immune suppressor cells in response to HIV-1 replication in the cervical tissues.

Original languageEnglish (US)
Pages (from-to)357-364
Number of pages8
JournalJournal of Acquired Immune Deficiency Syndromes
Volume67
Issue number4
DOIs
StatePublished - 2014

Keywords

  • CD8FOXP3 cells
  • Cytokines/chemokines
  • Genital shedding
  • HIV-1
  • Women

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

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