Albrecht, Christina

[["dc.bibliographiccitation.artnumber","600"],["dc.bibliographiccitation.journal","Frontiers in Immunology"],["dc.bibliographiccitation.volume","5"],["dc.contributor.author","Albrecht, Christina"],["dc.contributor.author","Brameier, Markus"],["dc.contributor.author","Hermes, Meike"],["dc.contributor.author","Ansari, Aftab A."],["dc.contributor.author","Walter, Lutz"],["dc.contributor.author","Malzahn, Dörthe"],["dc.date.accessioned","2018-11-07T09:32:24Z"],["dc.date.available","2018-11-07T09:32:24Z"],["dc.date.issued","2014"],["dc.description.abstract","Killer cell immunoglobulin-like receptors (KIR) regulate the activity of natural killer (NK) cells and have been shown to be associated with susceptibility to a number of human infectious diseases. Here, we analyzed NK cell function and genetic associations in a cohort of 52 rhesus macaques experimentally infected with SIVmac and subsequently stratified into high viral load (HVL) and low viral load (LVL) plasma viral loads at set point. This stratification coincided with fast (HVL) and slow (LVL) disease progression indicated by the disease course and critical clinical parameters including CD4+ T cell counts. HVL animals revealed sustained proliferation of NK cells but distinct loss of peripheral blood NK cell numbers and lytic function. Genetic analyses revealed that KIR genes 3DL05, 3DS05, and 3DL10 as well as 3DSW08, 3DLW03, and 3DSW09 are correlated, most likely due to underlying haplotypes. SIV-infection outcome associated with presence of transcripts for two inhibitory KIR genes (KIR3DL02, KIR3DL10) and three activating KIR genes (KIR3DSW08, KIR3DS02, KIR3DS05). Presence of KIR3DLO2 and KIR3DSW08 was associated with LVL outcome, whereas presence of KIR3DS02 was associated with HVL outcome. Furthermore, we identified epistasis between KIR and MHC class I alleles as the transcript presence of the correlated genes KIR3DL05, KIR3DS05, and KIR3DL10 increased HVL risk when Mamu-B 012 transcripts were also present or when Mamu-Al 001 transcripts were absent. These genetic associations were mirrored by changes in the numbers, the level of proliferation, and lytic capabilities of NK cells as well as overall survival time and gastro-intestinal tissue viral load."],["dc.description.sponsorship","NIH HHS [P51 OD011132]"],["dc.identifier.doi","10.3389/fimmu.2014.00600"],["dc.identifier.isi","000354531900001"],["dc.identifier.pmid","25506344"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/11789"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/31752"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Frontiers Media S.A."],["dc.relation.eissn","1664-3224"],["dc.relation.issn","1664-3224"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Progression to AIDS in SIV-infected rhesus macaques is associated with distinct KIR and MHC class 1 polymorphisms and NK cell dysfunction"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e1003929"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","PLoS Pathogens"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Takahashi, Yoshiaki"],["dc.contributor.author","Byrareddy, Siddappa N."],["dc.contributor.author","Albrecht, Christina"],["dc.contributor.author","Brameier, Markus"],["dc.contributor.author","Walter, Lutz"],["dc.contributor.author","Mayne, Ann E."],["dc.contributor.author","Dunbar, Paul"],["dc.contributor.author","Russo, Robert"],["dc.contributor.author","Little, Dawn M."],["dc.contributor.author","Villinger, Tara"],["dc.contributor.author","Khowawisetsut, Ladawan"],["dc.contributor.author","Pattanapanyasat, Kovit"],["dc.contributor.author","Villinger, Francois"],["dc.contributor.author","Ansari, Aftab A."],["dc.date.accessioned","2019-07-09T11:39:37Z"],["dc.date.available","2019-07-09T11:39:37Z"],["dc.date.issued","2014"],["dc.description.abstract","The studies reported herein are the first to document the effect of the in vivo administration of a JAK3 inhibitor for defining the potential role of NK cells during acute SIV infection of a group of 15 rhesus macaques (RM). An additional group of 16 MHC/KIR typed RM was included as controls. The previously optimized in vivo dose regimen (20 mg/kg daily for 35 days) led to a marked depletion of each of the major NK cell subsets both in the blood and gastro-intestinal tissues (GIT) during acute infection. While such depletion had no detectable effects on plasma viral loads during acute infection, there was a significant sustained increase in plasma viral loads during chronic infection. While the potential mechanisms that lead to such increased plasma viral loads during chronic infection remain unclear, several correlates were documented. Thus, during acute infection, the administration of the JAK3 inhibitor besides depleting all NK cell subsets also decreased some CD8+ T cells and inhibited the mobilization of the plasmacytoid dendritic cells in the blood and their localization to the GIT. Of interest is the finding that the administration of the JAK3 inhibitor during acute infection also resulted in the sustained maintenance during chronic infection of a high number of naïve and central memory CD4+ T cells, increases in B cells in the blood, but decreases in the frequencies and function of NKG2a+ NK cells within the GIT and blood, respectively. These data identify a unique role for JAK3 inhibitor sensitive cells, that includes NK cells during acute infection that in concert lead to high viral loads in SIV infected RM during chronic infection without affecting detectable changes in antiviral humoral/cellular responses. Identifying the precise mechanisms by which JAK3 sensitive cells exert their influence is critical with important implications for vaccine design against lentiviruses."],["dc.identifier.doi","10.1371/journal.ppat.1003929"],["dc.identifier.pmid","24603870"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10015"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58016"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1553-7374"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","In Vivo Administration of a JAK3 Inhibitor during Acute SIV Infection Leads to Significant Increases in Viral Load during Chronic Infection"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]