title: Differential CD4+ T-lymphocyte apoptosis and bystander T-cell activation in rhesus macaques and sooty mangabeys during acute simian immunodeficiency virus infection.
abstract: In contrast to pathogenic lentiviral infections, chronic simian immunodeficiency virus (SIV) infection in its natural host is characterized by a lack of increased immune activation and apoptosis. To determine whether these differences are species specific and predicted by the early host response to SIV in primary infection, we longitudinally examined T-lymphocyte apoptosis, immune activation, and the SIV-specific cellular immune response in experimentally infected rhesus macaques (RM) and sooty mangabeys (SM) with controlled or uncontrolled SIV infection. SIVsmE041, a primary SIVsm isolate, reproduced set-point viremia levels of natural SIV infection in SM but was controlled in RM, while SIVmac239 replicated to high levels in RM. Following SIV infection, increased CD8(+) T-lymphocyte apoptosis, temporally coinciding with onset of SIV-specific cellular immunity, and elevated plasma Th1 cytokine and gamma interferon-induced chemokine levels were common to both SM and RM. Different from SM, SIV-infected RM showed a significantly higher frequency of peripheral blood activated CD8(+) T lymphocytes despite comparable magnitude of the SIV-specific gamma interferon enzyme-linked immunospot response. Furthermore, an increase in CD4(+) and CD4(-)CD8(-) T-lymphocyte apoptosis and plasma tumor necrosis factor-related apoptosis-inducing ligand were observed only in RM and occurred in both controlled SIVsmE041 and uncontrolled SIVmac239 infection. These data suggest that the "excess" activated T lymphocytes in RM soon after SIV infection are predominantly of non-virus-specific bystander origin. Thus, species-specific differences in the early innate immune response appear to be an important factor contributing to differential immune activation in natural and nonnatural hosts of SIV infection.
authors.affiliation: Divisions of Immunology, New England Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772, USA.
authors.forename: Mareike
authors.initials: M
authors.lastname: Meythaler
authors.forename: Amanda
authors.initials: A
authors.lastname: Martinot
authors.forename: Zichun
authors.initials: Z
authors.lastname: Wang
authors.forename: Sarah
authors.initials: S
authors.lastname: Pryputniewicz
authors.forename: Melissa
authors.initials: M
authors.lastname: Kasheta
authors.forename: Binhua
authors.initials: B
authors.lastname: Ling
authors.forename: Preston A
authors.initials: PA
authors.lastname: Marx
authors.forename: Shawn
authors.initials: S
authors.lastname: O'Neil
authors.forename: Amitinder
authors.initials: A
authors.lastname: Kaur
mesh_terms: D000818:Animals; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016665:Cercocebus atys; D016207:Cytokines / Q000097:blood; D008213:Lymphocyte Activation; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D019562:Viral Load; D014766:Viremia
chemical_list: D016207:Cytokines