G-CSF reduces IFN-gamma and IL-4 production by T cells after allogeneic stimulation by indirectly modulating monocyte function.
Despite a 10-fold increase of T cell dose, the incidence and severity of acute GVHD following allogeneic transplantation of G-CSF-mobilized PBSC is not increased compared to BMT. Experimental murine studies demonstrate that G-CSF polarizes donor T cells toward a type 2 cytokine response. To determine whether G-CSF alters T cell cytokine responses, we investigated the effects of G-CSF administration on T cell proliferative and cytokine responses to alloantigen and Con A in nonadherent PBMC (NAC) and CD3+ T cells obtained from normal individuals before and after G-CSF administration (10 microg/kg x 4 days). Although T cell proliferative and cytokine (IFN-gamma and IL-4) responses to alloantigen stimulation and Con A were significantly reduced in post-G-CSF NAC, they were restored by the removal of non-T cells from post-G-CSF NAC. Furthermore, there was less T cell alloreactivity in MLR in the presence of autologous post-G-CSF monocytes than in the presence of pre-G-CSF monocytes. This alteration was not replicated in vitro by culturing PBMC with G-CSF. These results suggest that G-CSF administration suppresses T cell proliferative and cytokine (IFN-gamma and IL-4) responses to allogeneic stimulation by indirectly modulating monocyte function. Bone Marrow Transplantation (2000).
Nawa
Y
Y
Second Department of Medicine, Okayama University Medical School, Okayama, Japan.
Teshima
T
T
Sunami
K
K
Hiramatsu
Y
Y
Maeda
Y
Y
Yano
T
T
Shinagawa
K
K
Ishimaru
F
F
Omoto
E
E
Harada
M
M
D000328:Adult; D002478:Cells, Cultured; D018920:Coculture Techniques; D003208:Concanavalin A / Q000494:pharmacology; D003864:Depression, Chemical; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006086:Graft vs Host Disease / Q000209:etiology / Q000473:pathology; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000235:genetics; D007519:Isoantigens / Q000276:immunology*; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008212:Lymphocyte Depletion; D008297:Male; D009000:Monocytes / Q000187:drug effects* / Q000502:physiology; D015846:Monokines / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000378:metabolism*; D014184:Transplantation, Homologous
D007519:Isoantigens; D015846:Monokines; D011994:Recombinant Proteins; D003208:Concanavalin A; D016179:Granulocyte Colony-Stimulating Factor; D015847:Interleukin-4; D007371:Interferon-gamma