title: Noncytolytic CD8+ Cell Mediated Antiviral Response Represents a Strong Element in the Immune Response of Simian Immunodeficiency Virus-Infected Long-Term Non-Progressing Rhesus Macaques.
abstract: The ability of long term non progressors to maintain very low levels of HIV/SIV and a healthy state, involves various host genetic and immunological factors. CD8+ non-cytolytic antiviral response (CNAR) most likely plays an important role in this regard. In order to gain a deeper insight into this unique phenomenon, the ability of CD8+ T cells to suppress viral replication in vitro was investigated in 16 uninfected, longitudinally in 23 SIV-infected long-term non-progressing (LTNPs), and 10 SIV-infected rhesus macaques with progressing disease. An acute infection assay utilizing CD4+ cells from MHC-mismatched monkeys to avoid cytolytic responses was employed. The study has identified CNAR as a long-term stable activity that inversely correlated with plasma viral load. The activity was also detected in CD8+ cells of uninfected macaques, which indicates that CNAR is not necessarily a virus specific response but increases after SIV-infection. Physical contact between CD4+ and CD8+ cells was mainly involved in mediating viral inhibition. Loss of this activity appeared to be due to a loss of CNAR-expressing CD8+ cells as well as a reduction of CNAR-responsive CD4+ cells. In contrast, in vitro viral replication did not differ in CD4+ cells from un-infected macaques, CNAR(+) and CNAR(-) LTNPs. A role for transitional memory cells in supporting CNAR in the macaque model of AIDS was questionable. CNAR appears to represent an important part of the immune response displayed by CD8+ T cells which might be underestimated up to now.
authors.affiliation: Atta-ur-Rahman school of Applied Biosciences(ASAB), National University of Science and Technology (NUST), Islamabad, Pakistan.|Deutsches Primatenzentrum GmbH, Leibniz-Institut für Primatenforschung, Abteilung Infektionsmodelle, Göttingen, Germany.
authors.forename: Aneela
authors.initials: A
authors.lastname: Javed
authors.affiliation: Deutsches Primatenzentrum GmbH, Leibniz-Institut für Primatenforschung, Abteilung Infektionsmodelle, Göttingen, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Leuchte
authors.affiliation: Deutsches Primatenzentrum GmbH, Leibniz-Institut für Primatenforschung, Abteilung Infektionsmodelle, Göttingen, Germany.
authors.forename: Berit
authors.initials: B
authors.lastname: Neumann
authors.affiliation: Tumor Immunology Lab, Hematology and Oncology, Medical University Innsbruck and Tyrolean Cancer Research Institute, Innsbruck, Austria.
authors.forename: Sieghart
authors.initials: S
authors.lastname: Sopper
authors.affiliation: Deutsches Primatenzentrum GmbH, Leibniz-Institut für Primatenforschung, Abteilung Infektionsmodelle, Göttingen, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Sauermann
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018450:Disease Progression; D060467:Disease Resistance / Q000276:immunology; D007113:Immunity, Innate; D008253:Macaca mulatta / Q000276:immunology / Q000821:virology; D018448:Models, Immunological; D012367:RNA, Viral / Q000097:blood; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology / Q000502:physiology; D013997:Time Factors; D019562:Viral Load; D014779:Virus Replication / Q000276:immunology
chemical_list: D012367:RNA, Viral