PRETREATMENT OF DONOR MICE WITH GRANULOCYTE-COLONY-STIMULATING FACTORPOLARIZES DONOR T-LYMPHOCYTES TOWARD TYPE-2 CYTOKINE PRODUCTION AND REDUCES SEVERITY OF EXPERIMENTAL GRAFT-VERSUS-HOST DISEASE

The incidence and severity of acute graft-versus-host disease (GVHD) a fter allogeneic transplantation using peripheral blood progenitor cell s mobilized by granulocyte colony-stimulating factor IG-CSF) appear to be no worse than those after bone marrow transplantation, despite the presence of large numbers of T cells in the donor infusion. Experimen tal studies have shown that type-1 T cells (secreting interleukin-2 [I L-2] and interferon-gamma) mediate acute GVHD, whereas type-2 T cells (secreting IL-4 and IL-10) can prevent acute GVHD. We tested the hypot hesis that G-CSF modulates T-cell function toward a type-2 response an d thus reduces the severity of acute GVHD. B6 mice were injected with G-CSF or diluent for 4 days, and their splenic T cells were stimulated in vitro with alloantigen or mitogen in the absence of G-CSF. T cells from G-CSF-treated mice showed a significant increase in IL-4 product ion, with a simultaneous decrease in IL-2 and interferon-gamma product ion in response to both stimuli. We also examined the effect of G-CSF pretreatment of donors in a GVHD model (B6 --> B6D2F1). Survival was s ignificantly improved in recipients of G-CSF-treated donors. Concanava lin-A-induced cytokine production at day 13 after transplantation also showed an increase in IL-4 along with a decrease in IL-2 and IFN-gamm a production by splenocytes from recipients of G-CSF-treated bone marr ow and T cells. These data show that pretreatment of donors with G-CSF polarizes donor T cells toward the production of type-2 cytokines, wh ich is associated with reduced type-1 cytokine production and reduced severity of acute GVHD. (C) 1996 by The American Society of Hematology .