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Artículo

Intracellular expression of MICA in activated CD4 T lymphocytes and protection from NK cell-mediated MICA-dependent cytotoxicity.

Molinero, Luciana LorenaIcon ; Domaica, Carolina InesIcon ; Fuertes, Mercedes BeatrizIcon ; Girart, Maria VictoriaIcon ; Rossi, Lucas EzequielIcon ; Zwirner, Norberto WalterIcon
Fecha de publicación: 12/2006
Editorial: Karger
Revista: Human Immunology
ISSN: 0198-8859
e-ISSN: 1879-1166
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Inmunología

Resumen

MICA is a stress-regulated molecule recognized by the NK cell-activating receptor NKG2D. Previously, we demonstrated that MICA is induced on activated T cells but regulation by mitogenic cytokines and its biological consequences remain unexplored. Here, we show that IL-2, IL-4, and IL-15 but not TNF-alpha or IFN-alpha induced MICA expression in T lymphocytes present in peripheral blood mononuclear cells (PBMCs), as assessed by Western blot. IL-2 effect involved Jak3/STAT5, p38 MAPK, p70(56) kinase, Lck/fyn kinases, and NF-kappaB. MICA expression was also observed in Th1 and Th2 cells. However, surface expression was not detected. T lymphocytes present in PBMCs and isolated CD4+ T lymphocytes stimulated with phorbol-12-myristate-13-acetate and ionomycin also induced MICA expression as assessed by Western blot, but only low levels were expressed at the cell surface. Activated but not resting CD4+ T lymphocytes were lysed by IL-15- or IL-2-stimulated NK cells, and susceptibility was increased when HLA class I molecules were blocked. Also, cytokine-stimulated NK cells produced more IFN-gamma after culture with activated CD4+ T lymphocytes. However, the participation of MICA in these responses, if any, was marginal. Confocal microscopy revealed that MICA is retained mostly inside activated CD4+ T cells. Our results suggest that low surface expression of MICA on activated CD4+ T lymphocytes might be a safeguard mechanism to protect them from NK cells in an inflammatory, virus-infected, or tumor microenvironment, where NK and activated CD4+ T cells are recruited.
Palabras clave: Mica , Cd4 T Limphocytes , Nk Cells
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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Atribución-NoComercial-SinDerivadas 2.5 Argentina (CC BY-NC-ND 2.5 AR)
Identificadores
URI: http://hdl.handle.net/11336/28963
URL: http://www.sciencedirect.com/science/article/pii/S0198885906000310?via%3Dihub
DOI: http://dx.doi.org/10.1016/j.humimm.2006.02.010
Colecciones
Articulos(IBYME)
Articulos de INST.DE BIOLOGIA Y MEDICINA EXPERIMENTAL (I)
Articulos(SEDE CENTRAL)
Articulos de SEDE CENTRAL
Citación
Molinero, Luciana Lorena; Domaica, Carolina Ines; Fuertes, Mercedes Beatriz; Girart, Maria Victoria; Rossi, Lucas Ezequiel; et al.; Intracellular expression of MICA in activated CD4 T lymphocytes and protection from NK cell-mediated MICA-dependent cytotoxicity.; Karger; Human Immunology; 67; 3; 12-2006; 170-182
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