title: A distinct subset of human NK cells expressing HLA-DR expand in response to IL-2 and can aid immune responses to BCG.
abstract: Subsets of NK cells can have distinct functions. Here, we report that >25% of human peripheral blood NK cells express HLA-DR after culture with IL-2. This can be driven by an expansion of a small subset of NK cells expressing HLA-DR, in contrast to previous assumptions that HLA-DR is upregulated on previously negative cells. HLA-DR-expressing NK cells showed enhanced degranulation to susceptible target cells and expressed chemokine receptor CXCR3, which facilitated their enrichment following exposure to CXCL11/I-TAC. Suggesting HLA-DR-expressing NK cells have an important role in an immune response, stimulation of PBMCs with Mycobacterium bovis BCG (BCG) triggered expansion of this subset. Importantly, the magnitude of an individual's NK cell IFN-γ response triggered by BCG was associated with the initial frequency of HLA-DR-expressing NK cells in PBMCs. More directly indicating the importance of HLA-DR-expressing NK cells, enriching the frequency of this subset in PBMCs substantially augmented the IFN-γ response to BCG. Thus, HLA-DR expression marks a distinct subset of NK cells, present at low frequency in circulating blood but readily expanded by IL-2, that can play an important role during immune responses to BCG.
authors.affiliation: Division of Cell and Molecular Biology, Imperial College London, South Kensington Campus, London, UK. evans01@fas.harvard.edu
authors.forename: J Henry
authors.initials: JH
authors.lastname: Evans
authors.forename: Amir
authors.initials: A
authors.lastname: Horowitz
authors.forename: Maryam
authors.initials: M
authors.lastname: Mehrabi
authors.forename: Emma L
authors.initials: EL
authors.lastname: Wise
authors.forename: James E
authors.initials: JE
authors.lastname: Pease
authors.forename: Eleanor M
authors.initials: EM
authors.lastname: Riley
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Davis
mesh_terms: D019002:CD56 Antigen / Q000032:analysis; D002450:Cell Communication; D015550:Cell Degranulation; D054371:Chemokine CXCL11 / Q000276:immunology; D002634:Chemotaxis, Leukocyte; D006684:HLA-DR Antigens / Q000032:analysis*; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets / Q000276:immunology; D009163:Mycobacterium bovis / Q000276:immunology*; D054367:Receptors, CXCR3 / Q000276:immunology
chemical_list: D019002:CD56 Antigen; C515202:CXCL11 protein, human; C515187:CXCR3 protein, human; D054371:Chemokine CXCL11; D006684:HLA-DR Antigens; D007376:Interleukin-2; D054367:Receptors, CXCR3