title: HIV replication in conjunction with granzyme B production by CCR5+ memory CD4 T cells: Implications for bystander cell and tissue pathologies.
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.
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.
authors.forename: Jacob
authors.initials: J
authors.lastname: Couturier
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.
authors.forename: Alexander T
authors.initials: AT
authors.lastname: Hutchison
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Medina
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Cosmina
authors.initials: C
authors.lastname: Gingaras
authors.affiliation: Texas Children׳s Microbiome Center, Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Petri
authors.initials: P
authors.lastname: Urvil
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Chi
authors.initials: C
authors.lastname: Nguyen
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.
authors.forename: Parag
authors.initials: P
authors.lastname: Mahale
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Lin
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Claudia A
authors.initials: CA
authors.lastname: Kozinetz
authors.affiliation: Center for Virology and Vaccine Research, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
authors.forename: Joern E
authors.initials: JE
authors.lastname: Schmitz
authors.affiliation: Department of Molecular Virology & Microbiology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Jason T
authors.initials: JT
authors.lastname: Kimata
authors.affiliation: Texas Children׳s Microbiome Center, Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Tor C
authors.initials: TC
authors.lastname: Savidge
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA. Electronic address: Dorothy.E.Lewis@uth.tmc.edu.
authors.forename: Dorothy E
authors.initials: DE
authors.lastname: Lewis
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000378:metabolism* / Q000821:virology*; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D053804:Granzymes / Q000378:metabolism*; D006678:HIV / Q000502:physiology*; D006801:Humans; D017493:Leukocyte Common Antigens / Q000032:analysis; D008253:Macaca mulatta; D019713:Receptors, CCR5 / Q000032:analysis*; D018417:Th1 Cells / Q000378:metabolism / Q000821:virology; D058504:Th17 Cells / Q000378:metabolism / Q000821:virology; D014779:Virus Replication
chemical_list: C584933:CCR5 protein, human; D019713:Receptors, CCR5; D017493:Leukocyte Common Antigens; D053804:Granzymes
keywords: CCR5; Enteropathy; Granzyme B; HIV replication; Memory CD4 T cells; SIV pathogenesis