Granulocyte colony-stimulating factor modulates α-galactosylceramide-responsive human Vα24+ Vβ11+ NKT cells

T Crough, M Nieda, AJ Nicol - The Journal of Immunology, 2004 - journals.aai.org
T Crough, M Nieda, AJ Nicol
The Journal of Immunology, 2004journals.aai.org
Despite more than a 10-fold increase in T cell numbers in G-CSF-mobilized peripheral blood
stem cell (PBSC) grafts, incidence and severity of acute graft-vs-host disease (GVHD) are
comparable to bone marrow transplantation. As CD1d-restricted, Vα24+ Vβ11+ NKT cells
have pivotal immune regulatory functions and may influence GVHD, we aimed to determine
whether G-CSF has any effects on human NKT cells. In this study, we examined the
frequency and absolute numbers of peripheral blood NKT cells in healthy stem cell donors …
Abstract
Despite more than a 10-fold increase in T cell numbers in G-CSF-mobilized peripheral blood stem cell (PBSC) grafts, incidence and severity of acute graft-vs-host disease (GVHD) are comparable to bone marrow transplantation. As CD1d-restricted, Vα24+ Vβ11+ NKT cells have pivotal immune regulatory functions and may influence GVHD, we aimed to determine whether G-CSF has any effects on human NKT cells. In this study, we examined the frequency and absolute numbers of peripheral blood NKT cells in healthy stem cell donors (n= 8) before and following G-CSF (filgrastim) treatment. Effects of in vivo and in vitro G-CSF on NKT cell cytokine expression profiles and on responsiveness of NKT cell subpopulations to specific stimulation by α-galactosylceramide (α-GalCer) were assessed. Contrary to the effects on conventional T cells, the absolute number of peripheral blood NKT cells was unaffected by G-CSF administration. Furthermore, responsiveness of NKT cells to α-GalCer stimulation was significantly decreased (p< 0.05) following exposure to G-CSF in vivo. This hyporesponsiveness was predominantly due to a direct effect on NKT cells, with a lesser contribution from G-CSF-mediated changes in APC. G-CSF administration resulted in polarization of NKT cells toward a Th2, IL-4-secreting phenotype following α-GalCer stimulation and preferential expansion of the CD4+ NKT cell subset. We conclude that G-CSF has previously unrecognized differential effects in vivo on NKT cells and conventional MHC-restricted T cells, and effects on NKT cells may contribute to the lower than expected incidence of GVHD following allogeneic peripheral blood stem cell transplantation.
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