title: LFA-1 Activation in NK Cells and Their Subsets: Influence of Receptors, Maturation, and Cytokine Stimulation.
abstract: The integrin LFA-1 is essential for efficient activation and for cytotoxicity of NK cells because it initiates the assembly of the immunological synapse and mediates firm adhesion to the target. LFA-1 is also needed to polarize the cytotoxic machinery of the NK cell toward the target cell. The binding affinity and avidity of integrins can be regulated via inside-out signals from other receptors. In this article, we investigate the signals necessary to activate LFA-1 in human NK cells. Our data show that LFA-1 has a low ligand-binding activity in resting human NK cells, but it can be stimulated by triggering activating receptors, such as 2B4 or CD16, or by coactivation of different receptor combinations. Short-term stimulation of freshly isolated NK cells with cytokines, such as IL-15, IL-12, or IL-18, does not activate LFA-1 but increases the responsiveness of the cells to subsequent receptor stimulation. Different NK cell subsets vary in their ability to induce LFA-1 binding activity after activating receptor stimulation. Interestingly, the NK cell subsets that are more mature and possess higher cytotoxic potential also show the highest activation of LFA-1, which correlated with the expression of the small calcium-binding protein S100A4. Our data suggest that regulation of LFA-1 is one reason for the different activity of NK cells during differentiation.
authors.affiliation: Department of Immunology, Leibniz Research Centre for Working Environment and Human Factors at Technical University Dortmund-IfADo, 44139 Dortmund, Germany; and.
authors.forename: Doris
authors.initials: D
authors.lastname: Urlaub
authors.affiliation: Institute for Immunology, University Hospital Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Kristine
authors.initials: K
authors.lastname: Höfer
authors.affiliation: Institute for Immunology, University Hospital Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Martha-Lena
authors.identifier: 0000-0003-4391-9124
authors.initials: ML
authors.lastname: Müller
authors.affiliation: Department of Immunology, Leibniz Research Centre for Working Environment and Human Factors at Technical University Dortmund-IfADo, 44139 Dortmund, Germany; and watzl@ifado.de.
authors.forename: Carsten
authors.identifier: 0000-0001-5195-0995
authors.initials: C
authors.lastname: Watzl
mesh_terms: D002352:Carrier Proteins / Q000276:immunology; D002454:Cell Differentiation; D016207:Cytokines / Q000235:genetics / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D058851:GPI-Linked Proteins / Q000276:immunology; D005786:Gene Expression Regulation; D006801:Humans; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology; D019409:Interleukin-15 / Q000235:genetics / Q000276:immunology; D020382:Interleukin-18 / Q000235:genetics / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology / Q000502:physiology*; D008213:Lymphocyte Activation / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D017452:Receptors, IgG / Q000276:immunology; D015398:Signal Transduction
chemical_list: D002352:Carrier Proteins; D016207:Cytokines; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D019409:Interleukin-15; D020382:Interleukin-18; D016169:Lymphocyte Function-Associated Antigen-1; D017452:Receptors, IgG; D018664:Interleukin-12