title: Virus-specific CD8+ T cells upregulate programmed death-1 expression during acute friend retrovirus infection but are highly cytotoxic and control virus replication.
abstract: It was recently reported that inhibitory molecules such as programmed death-1 (PD-1) were upregulated on CD8(+) T cells during acute Friend retrovirus infection and that the cells were prematurely exhausted and dysfunctional in vitro. The current study confirms that most activated CD8(+) T cells upregulated expression of PD-1 during acute infection and revealed a dichotomy of function between PD-1(hi) and PD-1(lo) subsets. More PD-1(lo) cells produced antiviral cytokines such as IFN-γ and TNF-α, whereas more PD-1(hi) cells displayed characteristics of cytotoxic effectors such as production of granzymes and surface expression of CD107a. Importantly, CD8(+) T cells mediated rapid in vivo cytotoxicity and were critical for control of acute Friend virus replication. Thus, direct ex vivo analyses and in vivo experiments revealed high CD8(+) T cell functionality and indicate that PD-1 expression during acute infection is not a marker of T cell exhaustion.
authors.affiliation: Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen 45122, Germany.
authors.forename: Gennadiy
authors.initials: G
authors.lastname: Zelinskyy
authors.forename: Lara
authors.initials: L
authors.lastname: Myers
authors.forename: Kirsten K
authors.initials: KK
authors.lastname: Dietze
authors.forename: Kathrin
authors.initials: K
authors.lastname: Gibbert
authors.forename: Michael
authors.initials: M
authors.lastname: Roggendorf
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.forename: Mengji
authors.initials: M
authors.lastname: Lu
authors.forename: Anke R
authors.initials: AR
authors.lastname: Kraft
authors.forename: Volker
authors.initials: V
authors.lastname: Teichgräber
authors.forename: Kim J
authors.initials: KJ
authors.lastname: Hasenkrug
authors.forename: Ulf
authors.initials: U
authors.lastname: Dittmer
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002469:Cell Separation; D005434:Flow Cytometry; D005622:Friend murine leukemia virus / Q000276:immunology; D007942:Leukemia, Experimental / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D061026:Programmed Cell Death 1 Receptor / Q000096:biosynthesis* / Q000276:immunology; D012192:Retroviridae Infections / Q000276:immunology* / Q000378:metabolism; D014412:Tumor Virus Infections / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor