The corticosteroid-induced inhibitory effect on NK cell function reflects down-regulation and/or dysfunction of triggering receptors involved in natural cytotoxicity

Chiara Vitale, Laura Chiossone, Claudia Cantoni, Giuseppe Morreale, Francesca Cottalasso, Sara Moretti, Angela Pistorio, Riccardo Haupt, Edoardo Lanino, Giorgio Dini, Lorenzo Moretta, Maria Cristina Mingari

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Abstract

Corticosteroids are known to inhibit NK cell functions. However no information is available on whether such inhibition may affect the expression and/or the function of receptors involved in NK cell activation. In an attempt to analyze this point, we studied peripheral blood NK cells isolated from pediatric patients undergoing allogeneic BM transplantation. NK cells were analyzed before, during and after methylprednisolone administration to treat acute graft-versus-host disease. In NK cells freshly isolated from peripheral blood during methylprednisolone treatment, the surface expression of activating receptors, particularly NKp46 and NKp30, was consistently reduced. Such impaired expression could also be detected after 5 days of culture in IL-2. Such cultured NK cells also failed to express the IL-2-inducible NKp44 receptor. Accordingly, cytotoxicity against different tumor target cell lines was sharply reduced. The effect on NK cells isolated from healthy individuals and cultured in the presence of methylprednisolone was also analyzed. A similar inhibitory effect occurred in the expression of activating NK receptors. In addition, a sharp impairment of NK cytotoxicity against different tumor target cell lines or immature DC was detected.

Original languageEnglish
Pages (from-to)3028-3038
Number of pages11
JournalEuropean Journal of Immunology
Volume34
Issue number11
DOIs
Publication statusPublished - Nov 2004

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Natural Killer Cells
Adrenal Cortex Hormones
Down-Regulation
Methylprednisolone
Tumor Cell Line
Natural Cytotoxicity Triggering Receptor 2
Interleukin-2
Natural Cytotoxicity Triggering Receptor 3
Natural Cytotoxicity Triggering Receptor 1
Homologous Transplantation
Graft vs Host Disease
Cultured Cells
Blood Cells
Pediatrics

Keywords

  • Activating receptors
  • Bone marrow transplantation
  • Corticosteroids
  • Immunosuppression
  • NK cells

ASJC Scopus subject areas

  • Immunology

Cite this

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abstract = "Corticosteroids are known to inhibit NK cell functions. However no information is available on whether such inhibition may affect the expression and/or the function of receptors involved in NK cell activation. In an attempt to analyze this point, we studied peripheral blood NK cells isolated from pediatric patients undergoing allogeneic BM transplantation. NK cells were analyzed before, during and after methylprednisolone administration to treat acute graft-versus-host disease. In NK cells freshly isolated from peripheral blood during methylprednisolone treatment, the surface expression of activating receptors, particularly NKp46 and NKp30, was consistently reduced. Such impaired expression could also be detected after 5 days of culture in IL-2. Such cultured NK cells also failed to express the IL-2-inducible NKp44 receptor. Accordingly, cytotoxicity against different tumor target cell lines was sharply reduced. The effect on NK cells isolated from healthy individuals and cultured in the presence of methylprednisolone was also analyzed. A similar inhibitory effect occurred in the expression of activating NK receptors. In addition, a sharp impairment of NK cytotoxicity against different tumor target cell lines or immature DC was detected.",
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T1 - The corticosteroid-induced inhibitory effect on NK cell function reflects down-regulation and/or dysfunction of triggering receptors involved in natural cytotoxicity

AU - Vitale, Chiara

AU - Chiossone, Laura

AU - Cantoni, Claudia

AU - Morreale, Giuseppe

AU - Cottalasso, Francesca

AU - Moretti, Sara

AU - Pistorio, Angela

AU - Haupt, Riccardo

AU - Lanino, Edoardo

AU - Dini, Giorgio

AU - Moretta, Lorenzo

AU - Mingari, Maria Cristina

PY - 2004/11

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N2 - Corticosteroids are known to inhibit NK cell functions. However no information is available on whether such inhibition may affect the expression and/or the function of receptors involved in NK cell activation. In an attempt to analyze this point, we studied peripheral blood NK cells isolated from pediatric patients undergoing allogeneic BM transplantation. NK cells were analyzed before, during and after methylprednisolone administration to treat acute graft-versus-host disease. In NK cells freshly isolated from peripheral blood during methylprednisolone treatment, the surface expression of activating receptors, particularly NKp46 and NKp30, was consistently reduced. Such impaired expression could also be detected after 5 days of culture in IL-2. Such cultured NK cells also failed to express the IL-2-inducible NKp44 receptor. Accordingly, cytotoxicity against different tumor target cell lines was sharply reduced. The effect on NK cells isolated from healthy individuals and cultured in the presence of methylprednisolone was also analyzed. A similar inhibitory effect occurred in the expression of activating NK receptors. In addition, a sharp impairment of NK cytotoxicity against different tumor target cell lines or immature DC was detected.

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