HIV replication in conjunction with granzyme B production by CCR5+ memory CD4 T cells: Implications for bystander cell and tissue pathologies

Jacob Couturier, Alexander T. Hutchison, Miguel A. Medina, Cosmina Gingaras, Petri Urvil, Xiaoying Yu, Chi Nguyen, Parag Mahale, Lin Lin, Claudia A. Kozinetz, Joern E. Schmitz, Jason T. Kimata, Tor C. Savidge, Dorothy E. Lewis

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Granzyme B (GrzB) is expressed by activated T cells and mediates cellular apoptosis. GrzB also acts as an extracellular protease involved in tissue degradation. We hypothesized that GrzB production from activated memory CD4 T cells may be associated with HIV pathogenesis. We found that stimulated memory CD4 T cells (via costimulation, cytokines, and TLR ligands) concomitantly produced GrzB and HIV. Both GrzB and HIV expression were mainly restricted to CCR5-expressing memory CD4+CD45RO+ T cells, including Th1 and Th17 subsets. Activated memory CD4 T cells also mediated tissue damage, such as disruption of intestinal epithelial monolayers. In non-human primates, CD4 T cells of rhesus macaques (pathogenic SIV hosts) expressed higher GrzB compared to African green monkeys (non-pathogenic SIV hosts). These results suggest that GrzB from CCR5+ memory CD4 T cells may have a role in cellular and tissue pathologies during HIV infection. •CCR5+ memory CD4 T cells release GrzB and HIV during HIV replication.•TCR activation, cytokines, and TLR agonists induce GrzB and HIV production.•CD4 T cells mediate cellular monolayer tissue damage during HIV infection.

Original languageEnglish (US)
Pages (from-to)175-188
Number of pages14
JournalVirology
Volume462-463
Issue number1
DOIs
StatePublished - Aug 2014

Keywords

  • CCR5
  • Enteropathy
  • Granzyme B
  • HIV replication
  • Memory CD4 T cells
  • SIV pathogenesis

ASJC Scopus subject areas

  • Virology

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  • Cite this

    Couturier, J., Hutchison, A. T., Medina, M. A., Gingaras, C., Urvil, P., Yu, X., Nguyen, C., Mahale, P., Lin, L., Kozinetz, C. A., Schmitz, J. E., Kimata, J. T., Savidge, T. C., & Lewis, D. E. (2014). HIV replication in conjunction with granzyme B production by CCR5+ memory CD4 T cells: Implications for bystander cell and tissue pathologies. Virology, 462-463(1), 175-188. https://doi.org/10.1016/j.virol.2014.06.008