Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6139947 | Virology | 2014 | 14 Pages |
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.
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Authors
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,