Expression of a variant of CD28 on a subpopulation of human NK cells: implications for B7-mediated stimulation of NK cells
| Autor: | Galea-Lauri J, Darling D, Shu Uin Gan, Krivochtchapov L, Kuiper M, Gäken J, Souberbielle B, Farzaneh F |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Adult
Antigens Differentiation T-Lymphocyte Cytotoxicity Immunologic Transcription Genetic T-Lymphocytes Immunology Epitopes T-Lymphocyte chemical and pharmacologic phenomena Cell Separation Lymphocyte Activation Mice CD28 Antigens Species Specificity Antigens CD HLA Antigens Tumor Cells Cultured Animals Humans Immunology and Allergy Lectins C-Type RNA Messenger Cells Cultured B-Lymphocytes Histocompatibility Antigens Class II Antibodies Monoclonal Receptors Interleukin-2 hemic and immune systems Middle Aged Coculture Techniques Lymphocyte Subsets Clone Cells Killer Cells Natural B7-1 Antigen Binding Sites Antibody Sarcoma Experimental K562 Cells |
| Zdroj: | Europe PubMed Central Scopus-Elsevier |
| Popis: | The ability of NK cells to kill tumor cells is controlled by a balance between activating and inhibitory signals transduced by distinct receptors. In murine tumor models, the costimulatory molecule B7.1 not only acts as a positive trigger for NK-mediated cytotoxicity but can also overcome negative signaling transduced by MHC class I molecules. In this study, we have evaluated the potential of human B7.1-CD28 interaction as an activating trigger for human blood NK cells. Using multiparameter flow cytometric analysis and a panel of different CD28 mAbs, we show that human peripheral blood NK cells (defined by CD56+, CD16+, and CD3− surface expression) express the CD28 costimulatory receptor, with its detection totally dependent on the mAb used. In addition, the level of CD28 varies among individuals and on different NK cell lines, irrespective of CD28 steady-state mRNA levels. By performing Ab binding studies on T cells, our data strongly suggest that binding of two of the anti-CD28 Abs (clones 9.3 and CD28.2) is to a different epitope to that recognized by clones L293 and YTH913.12, which is perhaps modified in the CD28 molecule expressed by the NK cells. We also show that B7.1 enhances the NK-mediated lysis of NK-sensitive but not of NK-resistant tumor cells and that this increased lysis is dependent on CD28-B7 interactions as shown by the ability of Abs to block this lysis. Coculture of the B7.1-positive NK-sensitive cells also led to the activation of the NK cells, as determined by the expression of CD69, CD25, and HLA class II. |
| Databáze: | OpenAIRE |
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