title: Functional impairment of CD8(+) T cells by regulatory T cells during persistent retroviral infection.
abstract: The establishment of viral persistence generally requires evasion of the host CD8(+) T cell response. Here we describe a form of evasion wherein the CD8(+) T cells are fully capable of recognizing their cognate antigen but their effector functions are suppressed by regulatory T cells. Virus-specific CD8(+) T cells adoptively transferred into mice persistently infected with Friend virus proliferated and appeared activated, but failed to produce IFNgamma or reduce virus loads. Cotransfer experiments revealed that a subpopulation of CD4(+) T cells from persistently infected mice suppressed IFNgamma production by the CD8(+) T cells. Treatment of persistently infected mice with anti-GITR antibody to ameliorate suppression by regulatory T cells significantly improved IFNgamma production by transferred CD8(+) T cells and allowed a significant reduction in viral loads. The results indicate that CD4(+) regulatory T cells contribute to viral persistence and demonstrate an immunotherapy for treating chronic retroviral infections.
authors.affiliation: Institut für Virologie des Universitätsklinikums, 45122 Essen, Germany.
authors.forename: Ulf
authors.initials: U
authors.lastname: Dittmer
authors.forename: Hong
authors.initials: H
authors.lastname: He
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Messer
authors.forename: Simone
authors.initials: S
authors.lastname: Schimmer
authors.forename: Anke R M
authors.initials: AR
authors.lastname: Olbrich
authors.forename: Claes
authors.initials: C
authors.lastname: Ohlen
authors.forename: Philip D
authors.initials: PD
authors.lastname: Greenberg
authors.forename: Ingunn M
authors.initials: IM
authors.lastname: Stromnes
authors.forename: Michihiro
authors.initials: M
authors.lastname: Iwashiro
authors.forename: Shimon
authors.initials: S
authors.lastname: Sakaguchi
authors.forename: Leonard H
authors.initials: LH
authors.lastname: Evans
authors.forename: Karin E
authors.initials: KE
authors.lastname: Peterson
authors.forename: Guojun
authors.initials: G
authors.lastname: Yang
authors.forename: Kim J
authors.initials: KJ
authors.lastname: Hasenkrug
mesh_terms: D000208:Acute Disease; D019264:Adoptive Transfer; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D018984:Epitopes, T-Lymphocyte / Q000235:genetics; D005622:Friend murine leukemia virus / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology; D053450:Glucocorticoid-Induced TNFR-Related Protein; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D017475:Receptors, Nerve Growth Factor / Q000037:antagonists & inhibitors / Q000276:immunology; D018124:Receptors, Tumor Necrosis Factor / Q000037:antagonists & inhibitors / Q000276:immunology; D012192:Retroviridae Infections / Q000276:immunology* / Q000821:virology; D014412:Tumor Virus Infections / Q000276:immunology / Q000821:virology; D017735:Virus Latency
chemical_list: D000906:Antibodies; D018984:Epitopes, T-Lymphocyte; D015683:Gene Products, gag; D053450:Glucocorticoid-Induced TNFR-Related Protein; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C106544:Tnfrsf18 protein, mouse; D007371:Interferon-gamma