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 language | English (US) |
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Pages (from-to) | 175-188 |
Number of pages | 14 |
Journal | Virology |
Volume | 462-463 |
Issue number | 1 |
DOIs | |
State | Published - Aug 2014 |
Keywords
- CCR5
- Enteropathy
- Granzyme B
- HIV replication
- Memory CD4 T cells
- SIV pathogenesis
ASJC Scopus subject areas
- Virology