title: Gag- and Nef-specific CD4+ T cells recognize and inhibit SIV replication in infected macrophages early after infection.
abstract: The precise immunological role played by CD4(+) T cells in retroviral infections is poorly defined. Here, we describe a new function of these cells, the elimination of retrovirus-infected macrophages. After experimental CD8(+) cell depletion, elite controlling macaques with set-point viral loads < or = 500 viral RNA copies/mL mounted robust Gag- and Nef-specific CD4(+) T cell responses during reestablishment of control with > or = 54% of all virus-specific CD4(+) T cells targeting these 2 proteins. Ex vivo, these simian immunodeficiency virus (SIV)-specific CD4(+) T cells neither recognized nor suppressed viral replication in SIV-infected CD4(+) T cells. In contrast, they recognized SIV-infected macrophages as early as 2 h postinfection because of presentation of epitopes derived from virion-associated Gag and Nef proteins. Furthermore, virus-specific CD4(+) T cells displayed direct effector function and eliminated SIV-infected macrophages. These results suggest that retrovirus-specific CD4(+) T cells may contribute directly to elite control by inhibiting viral replication in macrophages.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, WI 53715, USA. jbsacha@wisc.edu
authors.forename: Jonah B
authors.initials: JB
authors.lastname: Sacha
authors.forename: Juan P
authors.initials: JP
authors.lastname: Giraldo-Vela
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Buechler
authors.forename: Mauricio A
authors.initials: MA
authors.lastname: Martins
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Maness
authors.forename: Chungwon
authors.initials: C
authors.lastname: Chung
authors.forename: Lyle T
authors.initials: LT
authors.lastname: Wallace
authors.forename: Enrique J
authors.initials: EJ
authors.lastname: León
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Friedrich
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Wilson
authors.forename: Atsunobu
authors.initials: A
authors.lastname: Hiraoka
authors.forename: David I
authors.initials: DI
authors.lastname: Watkins
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015683:Gene Products, gag / Q000378:metabolism*; D015693:Gene Products, nef / Q000378:metabolism*; D008253:Macaca mulatta; D008264:Macrophages / Q000821:virology*; D012367:RNA, Viral / Q000097:blood; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D019562:Viral Load; D014779:Virus Replication / Q000276:immunology*
chemical_list: D015683:Gene Products, gag; D015693:Gene Products, nef; D012367:RNA, Viral