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Granulocyte–colony‐stimulatory factor: a strong inhibitor of natural killer cell function
Author(s) -
Schlahsa Laura,
Jaimes Yarúa,
Blasczyk Rainer,
Figueiredo Constança
Publication year - 2011
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/j.1537-2995.2010.02820.x
Subject(s) - granzyme b , biology , cytokine , natural killer cell , granulocyte , lymphokine activated killer cell , interleukin 12 , tumor necrosis factor alpha , haematopoiesis , interleukin 21 , in vivo , nkg2d , immunology , cytotoxicity , in vitro , stem cell , cytotoxic t cell , microbiology and biotechnology , immune system , t cell , biochemistry
BACKGROUND: The human cytokine granulocyte–colony stimulatory factor (G‐CSF) has found widespread application in the medical treatment of neutropenia and to mobilize hematopoietic stem cells used for transplantation. So far, the effect of G‐CSF on natural killer (NK) cells has not been fully investigated. STUDY DESIGN AND METHODS: The effect of G‐CSF on the phenotype, cytokine secretion profile, and cytotoxicity of NK cells was assessed. NK cells incubated in vitro in presence of G‐CSF for 48 hours as well as NK cells isolated from peripheral blood of G‐CSF–mobilized stem cell donors (in vivo) were used. RESULTS: In vitro, G‐CSF caused a strongly altered phenotype in NK cells with 49% down regulation of NKp44 frequency. Furthermore, the expression of the activating receptors NKp46 and NKG2D decreased 40 and 64%, respectively. The expression of KIR2DL1 and KIR2DL2 decreased by 46% each. In cytotoxicity assays, the lytic capacity of G‐CSF–exposed NK cells is reduced by up to 68% in vitro and up to 83% in vivo. Accordingly, granzyme B levels of in vivo G‐CSF–exposed NK cells were reduced by up to 87% in comparison to nonstimulated NK cells. Cytokine production of in vitro and in vivo incubated NK cells was strongly decreased for interferon‐γ, tumor necrosis factor‐α, and granulocyte macrophage colony‐stimulating factor as well as interleukin (IL)‐6 and IL‐8. Furthermore, we observed a reduction in proliferation and a positive feedback loop that increased the expression of the G‐CSF receptor. CONCLUSION: G‐CSF was demonstrated to be a strong inhibitor of NK cells activity and may prevent their graft‐versus‐leukemia effect after transplantation.