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  • 1
    Online Resource
    Online Resource
    CD8 T cells express randomly selected KIRs with distinct specificities compared to NK cells (P1418)
    The American Association of Immunologists ; 2013
    In:  The Journal of Immunology Vol. 190, No. 1_Supplement ( 2013-05-01), p. 117.9-117.9
    Details
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 190, No. 1_Supplement ( 2013-05-01), p. 117.9-117.9
    Abstract: Epistatic interactions between killer cell immunoglobulin-like receptors (KIRs) and their cognate HLA class I ligands have important implications for reproductive success, anti-viral immunity, susceptibility to autoimmune conditions and cancer, as well as for graft-versus-leukemia reactions in settings of allogeneic stem cell transplantation. Although CD8 T cells are known to acquire KIRs when maturing from naïve to terminally differentiated cells, little information is available about the constitution of KIR repertoires on human CD8 T cells. Here, we have performed a high-resolution analysis of KIR-expression on CD8 T cells. The results show that most CD8 T cells possess a restricted KIR expression-pattern, often dominated by a single activating or inhibitory KIR. Furthermore, the expression of KIR, and its modulation of CD8 T cell function, was independent of expression of self-HLA class I-ligands. Finally, despite similarities in the stochastic regulation of KIRs by the bi-directional proximal promoter, the specificity of inhibitory KIRs on CD8 T cells was often distinct from that of NK cells in the same individual. The results provide new insight into the formation of KIR repertoires on human T cells.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    URL: Article
    DOI: 10.4049/jimmunol.190.Supp.117.9
    RVK:
    XA 54100
    RVK:
    XA 10000
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2013
    detail.hit.zdb_id: 1475085-5
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  • 2
    Online Resource
    Online Resource
    Coordinated Expression of DNAM-1 and LFA-1 in Educated NK Cells
    The American Association of Immunologists ; 2015
    In:  The Journal of Immunology Vol. 194, No. 9 ( 2015-05-01), p. 4518-4527
    Details
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 194, No. 9 ( 2015-05-01), p. 4518-4527
    Abstract: The functional capacity of NK cells is dynamically tuned by integrated signals from inhibitory and activating cell surface receptors in a process termed NK cell education. However, the understanding of the cellular and molecular mechanisms behind this functional tuning is limited. In this study, we show that the expression of the adhesion molecule and activation receptor DNAX accessory molecule 1 (DNAM-1) correlates with the quantity and quality of the inhibitory input by HLA class I–specific killer cell Ig-like receptors and CD94/NKG2A as well as with the magnitude of functional responses. Upon target cell recognition, the conformational state of LFA-1 changed in educated NK cells, associated with rapid colocalization of both active LFA-1 and DNAM-1 at the immune synapse. Thus, the coordinated expression of LFA-1 and DNAM-1 is a central component of NK cell education and provides a potential mechanism for controlling cytotoxicity by functionally mature NK cells.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    URL: Article
    DOI: 10.4049/jimmunol.1401972
    RVK:
    XA 54100
    RVK:
    XA 10000
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2015
    detail.hit.zdb_id: 1475085-5
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  • 3
    Online Resource
    Online Resource
    Naive Donor NK Cell Repertoires Associated with Less Leukemia Relapse after Allogeneic Hematopoietic Stem Cell Transplantation
    The American Association of Immunologists ; 2016
    In:  The Journal of Immunology Vol. 196, No. 3 ( 2016-02-01), p. 1400-1411
    Details
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 196, No. 3 ( 2016-02-01), p. 1400-1411
    Abstract: Acute and latent human CMV cause profound changes in the NK cell repertoire, with expansion and differentiation of educated NK cells expressing self-specific inhibitory killer cell Ig-like receptors. In this study, we addressed whether such CMV-induced imprints on the donor NK cell repertoire influenced the outcome of allogeneic stem cell transplantation. Hierarchical clustering of high-resolution immunophenotyping data covering key NK cell parameters, including frequencies of CD56bright, NKG2A+, NKG2C+, and CD57+ NK cell subsets, as well as the size of the educated NK cell subset, was linked to clinical outcomes. Clusters defining naive (NKG2A+CD57−NKG2C−) NK cell repertoires in the donor were associated with decreased risk for relapse in recipients with acute myeloid leukemia and myelodysplastic syndrome (hazard ratio [HR], 0.09; 95% confidence interval [CI] : 0.03–0.27; p & lt; 0.001). Furthermore, recipients with naive repertoires at 9–12 mo after hematopoietic stem cell transplantation had increased disease-free survival (HR, 7.2; 95% CI: 1.6–33; p = 0.01) and increased overall survival (HR, 9.3; 95% CI: 1.1–77, p = 0.04). Conversely, patients with a relative increase in differentiated NK cells at 9–12 mo displayed a higher rate of late relapses (HR, 8.41; 95% CI: 6.7–11; p = 0.02), reduced disease-free survival (HR, 0.12; 95% CI: 0.12–0.74; p = 0.02), and reduced overall survival (HR, 0.07; 95% CI: 0.01–0.69; p = 0.02). Thus, our data suggest that naive donor NK cell repertoires are associated with protection against leukemia relapse after allogeneic HSCT.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    URL: Article
    DOI: 10.4049/jimmunol.1501434
    RVK:
    XA 54100
    RVK:
    XA 10000
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2016
    detail.hit.zdb_id: 1475085-5
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  • 4
    Online Resource
    Online Resource
    Cutting Edge: Identification and Characterization of Human Intrahepatic CD49a+ NK Cells
    The American Association of Immunologists ; 2015
    In:  The Journal of Immunology Vol. 194, No. 6 ( 2015-03-15), p. 2467-2471
    Details
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 194, No. 6 ( 2015-03-15), p. 2467-2471
    Abstract: Although NK cells are considered innate, recent studies in mice revealed the existence of a unique lineage of hepatic CD49a+DX5− NK cells with adaptive-like features. Development of this NK cell lineage is, in contrast to conventional NK cells, dependent on T-bet but not Eomes. In this study, we describe the identification of a T-bet+Eomes−CD49a+ NK cell subset readily detectable in the human liver, but not in afferent or efferent hepatic venous or peripheral blood. Human intrahepatic CD49a+ NK cells express killer cell Ig-like receptor and NKG2C, indicative of having undergone clonal-like expansion, are CD56bright, and express low levels of CD16, CD57, and perforin. After stimulation, CD49a+ NK cells express high levels of inflammatory cytokines but degranulate poorly. CD49a+ NK cells retain their phenotype after expansion in long-term in vitro cultures. These results demonstrate the presence of a likely human counterpart of mouse intrahepatic NK cells with adaptive-like features.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    URL: Article
    DOI: 10.4049/jimmunol.1402756
    RVK:
    XA 54100
    RVK:
    XA 10000
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2015
    detail.hit.zdb_id: 1475085-5
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  • 5
    Online Resource
    Online Resource
    CD56brightCD16+ NK Cells: A Functional Intermediate Stage of NK Cell Differentiation
    The American Association of Immunologists ; 2011
    In:  The Journal of Immunology Vol. 186, No. 12 ( 2011-06-15), p. 6753-6761
    Details
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 186, No. 12 ( 2011-06-15), p. 6753-6761
    Abstract: Human NK cells comprise two main subsets, CD56bright and CD56dim cells, which differ in function, phenotype, and tissue localization. To further dissect the differentiation from CD56bright to CD56dim cells, we performed ex vivo and in vitro experiments demonstrating that the CD56brightCD16+ cells are an intermediate stage of NK cell maturation. We observed that the maximal frequency of the CD56brightCD16+ subset among NK cells, following unrelated cord blood transplantation, occurs later than this of the CD56brightCD16− subset. We next performed an extensive phenotypic and functional analysis of CD56brightCD16+ cells in healthy donors, which displayed a phenotypic intermediary profile between CD56brightCD16− and CD56dimCD16+ NK cells. We also demonstrated that CD56brightCD16+ NK cells were fully able to kill target cells, both by Ab-dependent cell cytotoxicity (ADCC) and direct lysis, as compared with CD56brightCD16− cells. Importantly, in vitro differentiation experiments revealed that autologous T cells specifically encourage the differentiation from CD56brightCD16− to CD56brightCD16+ cells. Finally, further investigations performed in elderly patients clearly showed that both CD56brightCD16+ and CD56dimCD16+ mature subsets were substantially increased in older individuals, whereas the CD56brightCD16− precursor subset was decreased. Altogether, these data provide evidence that the CD56brightCD16+ NK cell subset is a functional intermediate between the CD56bright and CD56dim cells and is generated in the presence of autologous T CD3+ cells.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    URL: Article
    DOI: 10.4049/jimmunol.1100330
    RVK:
    XA 54100
    RVK:
    XA 10000
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2011
    detail.hit.zdb_id: 1475085-5
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