G-CSF inhibits LFA-1-mediated CD4+ T cell functions by inhibiting Lck and ZAP-70

Abstract

In this study, we showed that G-CSF mobilization increased the frequency of T cells, specifically CD3⁺CD4⁺ T cells. G-CSF mobilization decreased the secretion of inflammatory cytokines of CD4⁺ T cells through the LFA-1/ICAM-1 signaling pathway, whereas it did not alter the TH1/TH2 ratio. We found that G-CSF mobilization inhibited LFA-1-mediated CD4⁺ T cell polarization and motility. In vitro, G-CSF stimulation also attenuated the polarization and adhesiveness of CD4⁺ T cells through the LFA-1/ICAM-1 interaction. Further investigation revealed that G-CSF mobilization suppressed LFA-1 signaling by down-regulating Lck and ZAP-70 expression in CD4⁺ T cells, similar results was also confirmed by in-vitro studies. These findings suggested that G-CSF directly suppressed LFA-1-mediated CD4⁺ T cell functions through the down-regulation of Lck and ZAP-70. The immunosuppressive effect of G-CSF mobilization deepened our understanding about peripheral blood hematopoietic stem cell transplantation. LFA-1/ICMA-1 pathway may become a potential target for graft-versus-host disease prophylaxis.