Persistence of natural killer cells with expansion of a hypofunctional CD56−CD16+KIR+NKG2C+ subset in a patient with atypical Janus kinase 3–deficient.

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Persistence of natural killer cells with expansion of a hypofunctional CD56−CD16+KIR+NKG2C+ subset in a patient with atypical Janus kinase 3–deficient severe combined immunodeficiency Laure Farnault, MD, Hervé Chambost, MD, Gérard Michel, MD, Isabelle Thuret, MD, Geneviève de Saint Basile, MD, Alain Fischer, MD, PhD, Capucine Picard, MD, PhD, Christophe Picard, MD, Florence Orlanducci, Catherine Farnarier, MD, Alessandro Moretta, MD, PhD, Daniel Olive, MD, PhD Journal of Allergy and Clinical Immunology Volume 131, Issue 4, Pages 1230-1233.e2 (April 2013) DOI: 10.1016/j.jaci.2012.08.047 Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Phenotypic characteristics of NK cell subsets. A, Dot plots show NK cell subsets as defined by CD56 and CD16 expression in our patient and in representative age-matched control subjects. The represented cells were gated on CD3− lymphocytes. B, Histograms of CD158b, NKG2A, NKG2C, and Siglec-7 expression on the CD56−CD16+ NK cell subset of patient. C, Graphs summarizing the expression of various markers in CD56−CD16+ and CD56dimCD16+ NK cell subsets of the patient (black bars) and control subjects (white bars; n = 4 age-matched healthy volunteers). D, Dot plot showing the expression of CD56 and Siglec-7 in NK cells of our patient and of a representative control subject. Cells were gated on Siglec-7-aminoactinomycin D–negative, CD19−, CD14−, and CD3− lymphocytes. Journal of Allergy and Clinical Immunology 2013 131, 1230-1233.e2DOI: (10.1016/j.jaci.2012.08.047) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Functional capacity of CD56dimCD16+ and CD56−CD16+ NK cell subsets. The degranulation activity (A) and cytokine secretion capacity (B) of CD56dimCD16+ and CD56−CD16+ NK cell subsets of the patient (black bars) and the control group (n = 3, gray bars) are shown. The graph represents the percentage of degranulation measured by using CD107 expression of NK subsets after stimulation with the negative control P815, K562, and P815 coated with anti-CD16 mAb. C, Histograms of IFN-γ secretion and CD107 expression by CD56−CD16+ and CD56dimCD16+ NK cell subsets after stimulation with P815 coated with anti-NKG2C mAb. Journal of Allergy and Clinical Immunology 2013 131, 1230-1233.e2DOI: (10.1016/j.jaci.2012.08.047) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 Functionality of JAK3 protein. A, Histogram of JAK3 protein expression on NK cells of the patient and his mother. B, NK cell activation through IL-2 and IL-15 stimulation through the JAK3 and subsequently signal transducer and activator of transcription 5 pathway. Histograms show increased expression of the proliferation-associated molecule Ki67, upregulation of NKp44, and increased cell division evaluated with Cell Trace (Invitrogen, Carlsbad, Calif) in the patient’s mother's NK cells conversely to the patient’s NK cells, which exhibited only weak or no response to IL-2 plus IL-15 stimulation. Journal of Allergy and Clinical Immunology 2013 131, 1230-1233.e2DOI: (10.1016/j.jaci.2012.08.047) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions