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Two populations of human natural killer (NK) cells can be identified in peripheral blood. The majority are CD3-CD56dim cells while the minority exhibits a CD3-CD56bright phenotype. In vitro evidence indicates that CD56bright cells are precursors of CD56dim cells, but in vivo evidence is lacking. Here, we studied NK cells from a patient that suffered from a melanoma and opportunistic fungal infection during childhood. The patient exhibited a stable phenotype characterized by a reduction in the frequency of peripheral blood CD3-CD56dim NK cells, accompanied by an overt increase in the frequency and absolute number of CD3-CD56bright cells. These NK cells exhibited similar expression of perforin, CD57 and CD158, the major activating receptors CD16, NKp46, NKG2D, DNAM-1, and 2B4, as well as the inhibitory receptor CD94/NKG2A, on both CD56bright and CD56dim NK cells as healthy controls. Also, both NK cell subpopulations produced IFN-γ upon stimulation with cytokines, and CD3-CD56dim NK cells degranulated in response to cytokines or K562 cells. However, upon stimulation with cytokines, a substantial fraction of CD56dim cells failed to up-regulate CD57 and CD158, showed a reduction in the percentage of CD16+ cells, and CD56bright cells did not down-regulate CD62L, suggesting that CD56dim cells could not acquire a terminally differentiated phenotype and that CD56bright cells exhibit a maturation defect that might result in a potential altered migration pattern. These observations, support the notion that NK cells of this patient display a maturation/activation defect that precludes the generation of mature NK cells at a normal rate accompanied by CD56dim NK cells that cannot completely acquire a terminally differentiated phenotype. Thus, our results provide evidence that support the concept that in vivo CD56bright NK cells differentiate into CD56dim NK cells, and contribute to further understand human NK cell ontogeny. © 2012 Domaica et al.


Documento: Artículo
Título:Human Natural Killer Cell Maturation Defect Supports In Vivo CD56bright to CD56dim Lineage Development
Autor:Domaica, C.I.; Fuertes, M.B.; Uriarte, I.; Girart, M.V.; Sardañons, J.; Comas, D.I.; Di Giovanni, D.; Gaillard, M.I.; Bezrodnik, L.; Zwirner, N.W.
Filiación:Laboratorio de Fisiopatología de la Inmunidad Innata, Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina
Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
Unidad de Inmunología, Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina
Departamento de Microbiología, Parasitología e Inmunología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina
Palabras clave:CD158 antigen; CD16 antigen; CD3 antigen; CD56 antigen; CD57 antigen; CD94 antigen; cell antigen; cell protein; gamma interferon; natural cytotoxicity triggering receptor 1; natural killer cell receptor NKG2A; natural killer cell receptor NKG2D; perforin; protein 2B4; protein DNAM 1; unclassified drug; adolescent; antigen expression; article; cell lineage; cell maturation; controlled study; cytokine response; down regulation; human; human cell; in vivo study; lymphocyte activation; lymphocyte differentiation; lymphocyte migration; lymphocyte subpopulation; melanoma; natural killer cell; opportunistic infection; phenotypic variation; protein expression; upregulation; Antigens, CD56; Cell Differentiation; Cell Lineage; Flow Cytometry; Humans; Interferon-gamma; K562 Cells; Killer Cells, Natural; Leukocytes, Mononuclear
Título revista:PLoS ONE
Título revista abreviado:PLoS ONE
CAS:gamma interferon, 82115-62-6; perforin, 119332-27-3; Antigens, CD56; Interferon-gamma, 82115-62-6; NCAM1 protein, human


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---------- APA ----------
Domaica, C.I., Fuertes, M.B., Uriarte, I., Girart, M.V., Sardañons, J., Comas, D.I., Di Giovanni, D.,..., Zwirner, N.W. (2012) . Human Natural Killer Cell Maturation Defect Supports In Vivo CD56bright to CD56dim Lineage Development. PLoS ONE, 7(12).
---------- CHICAGO ----------
Domaica, C.I., Fuertes, M.B., Uriarte, I., Girart, M.V., Sardañons, J., Comas, D.I., et al. "Human Natural Killer Cell Maturation Defect Supports In Vivo CD56bright to CD56dim Lineage Development" . PLoS ONE 7, no. 12 (2012).
---------- MLA ----------
Domaica, C.I., Fuertes, M.B., Uriarte, I., Girart, M.V., Sardañons, J., Comas, D.I., et al. "Human Natural Killer Cell Maturation Defect Supports In Vivo CD56bright to CD56dim Lineage Development" . PLoS ONE, vol. 7, no. 12, 2012.
---------- VANCOUVER ----------
Domaica, C.I., Fuertes, M.B., Uriarte, I., Girart, M.V., Sardañons, J., Comas, D.I., et al. Human Natural Killer Cell Maturation Defect Supports In Vivo CD56bright to CD56dim Lineage Development. PLoS ONE. 2012;7(12).