title: A novel SIV gag-specific CD4(+)T-cell clone suppresses SIVmac239 replication in CD4(+)T cells revealing the interplay between antiviral effector cells and their infected targets.
abstract: To study CD4(+)T-cell suppression of AIDS virus replication, we isolated nine rhesus macaque SIVGag-specific CD4(+)T-cell clones. One responding clone, Gag68, produced a typical cytotoxic CD8(+)T-cell response: induction of intracellular IFN-γ, MIP-1α, MIP-1β, and CD107a degranulation. Gag68 effectively suppressed the spread of SIVmac239 in CD4(+)T cells with a corresponding reduction of infected Gag68 effector cells, suggesting that CD4(+)effectors need to suppress their own infection in addition to their targets to be effective. Gag68 TCR cloning and gene transfer into CD4(+)T cells enabled additional experiments with this unique specificity after the original clone senesced. Our data supports the idea that CD4(+)T cells can directly limit AIDS virus spread in T cells. Furthermore, Gag68 TCR transfer into CD4(+)T-cell clones with differing properties holds promise to better understand the suppressive effector mechanisms used by this important component of the antiviral response using the rhesus macaque model.
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702-1201, USA.
authors.forename: Victor I
authors.initials: VI
authors.lastname: Ayala
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702-1201, USA.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Trivett
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702-1201, USA.
authors.forename: Lori V
authors.initials: LV
authors.lastname: Coren
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702-1201, USA.
authors.forename: Sumiti
authors.initials: S
authors.lastname: Jain
authors.affiliation: Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Bohn
authors.affiliation: Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: Roger W
authors.initials: RW
authors.lastname: Wiseman
authors.affiliation: Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: O'Connor
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702-1201, USA.
authors.forename: Claes
authors.initials: C
authors.lastname: Ohlen
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702-1201, USA. Electronic address: ottde@mail.nih.gov.
authors.forename: David E
authors.initials: DE
authors.lastname: Ott
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D002478:Cells, Cultured; D002999:Clone Cells; D015683:Gene Products, gag / Q000276:immunology; D008253:Macaca mulatta; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D015302:Simian Immunodeficiency Virus / Q000276:immunology / Q000502:physiology*; D037182:T-Cell Antigen Receptor Specificity; D014779:Virus Replication
chemical_list: D015683:Gene Products, gag; D011948:Receptors, Antigen, T-Cell
keywords: Cytolytic CD4(+)T cells; SIV; T-cell effectors; T-cell receptor; TCR transduction; Virus suppression; Virus-specific