Human Natural Killer Cell Maturation Defect Supports In Vivo CD56bright to CD56dim Lineage Development
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. Her...
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| Formato: | Artículo publishedVersion |
| Lenguaje: | Inglés |
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2012
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| Acceso en línea: | http://hdl.handle.net/20.500.12110/paper_19326203_v7_n12_p_Domaica |
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paperaa:paper_19326203_v7_n12_p_Domaica2023-06-12T16:51:35Z Human Natural Killer Cell Maturation Defect Supports In Vivo CD56bright to CD56dim Lineage Development PLoS ONE 2012;7(12) 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. 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 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. Fil:Domaica, C.I. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Fuertes, M.B. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Girart, M.V. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2012 info:eu-repo/semantics/article info:ar-repo/semantics/artículo info:eu-repo/semantics/publishedVersion application/pdf eng info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_19326203_v7_n12_p_Domaica |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| language |
Inglés |
| orig_language_str_mv |
eng |
| topic |
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 |
| spellingShingle |
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 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. Human Natural Killer Cell Maturation Defect Supports In Vivo CD56bright to CD56dim Lineage Development |
| topic_facet |
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 |
| description |
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. |
| format |
Artículo Artículo publishedVersion |
| author |
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. |
| author_facet |
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. |
| author_sort |
Domaica, C.I. |
| title |
Human Natural Killer Cell Maturation Defect Supports In Vivo CD56bright to CD56dim Lineage Development |
| title_short |
Human Natural Killer Cell Maturation Defect Supports In Vivo CD56bright to CD56dim Lineage Development |
| title_full |
Human Natural Killer Cell Maturation Defect Supports In Vivo CD56bright to CD56dim Lineage Development |
| title_fullStr |
Human Natural Killer Cell Maturation Defect Supports In Vivo CD56bright to CD56dim Lineage Development |
| title_full_unstemmed |
Human Natural Killer Cell Maturation Defect Supports In Vivo CD56bright to CD56dim Lineage Development |
| title_sort |
human natural killer cell maturation defect supports in vivo cd56bright to cd56dim lineage development |
| publishDate |
2012 |
| url |
http://hdl.handle.net/20.500.12110/paper_19326203_v7_n12_p_Domaica |
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