       Document 0128
 DOCN  M9640128
 TI    Pretreatment of donor mice with granulocyte colony-stimulating factor
       polarizes donor T lymphocytes toward type-2 cytokine production and
       reduces severity of experimental graft-versus-host disease.
 DT    9604
 AU    Pan L; Delmonte J Jr; Jalonen CK; Ferrara JL; Division of Pediatric
       Oncology, Dana Farber Cancer Institute,; Boston, MA 02115, USA.
 SO    Blood. 1995 Dec 15;86(12):4422-9. Unique Identifier : AIDSLINE
       MED/96127785
 AB    The incidence and severity of acute graft-versus-host disease (GVHD)
       after allogeneic transplantation using peripheral blood progenitor cells
       mobilized by granulocyte colony-stimulating factor (G-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. Experimental
       studies have shown that type-1 T cells (secreting interleukin-2 [IL-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
       hypothesis that G-CSF modulates T-cell function toward a type-2 response
       and 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
       production, with a simultaneous decrease in IL-2 and interferon-gamma
       production in response to both stimuli. We also examined the effect of
       G-CSF pretreatment of donors in a GVHD model (B6-->B6D2F1). Survival was
       significantly improved in recipients of G-CSF-treated donors.
       Concanavalin-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-gamma production by splenocytes from recipients of
       G-CSF-treated bone marrow and T cells. These data show that pretreatment
       of donors with G-CSF polarizes donor T cells toward the production of
       type-2 cytokines, which is associated with reduced type-1 cytokine
       production and reduced severity of acute GVHD.
 DE    Acute Disease  Animal  Biological Response Modifiers/ADMINISTRATION &
       DOSAGE/  *PHARMACOLOGY/THERAPEUTIC USE  Bone Marrow
       Transplantation/*ADVERSE EFFECTS  Cell Differentiation/DRUG EFFECTS
       Female  Graft vs Host Disease/ETIOLOGY/*PREVENTION & CONTROL
       Granulocyte Colony-Stimulating Factor/ADMINISTRATION & DOSAGE/
       *PHARMACOLOGY/THERAPEUTIC USE  Hematopoietic Stem Cell
       Transplantation/*ADVERSE EFFECTS  Human  Interleukin-4/BIOSYNTHESIS
       Lymphocyte Transformation  Mice  Mice, Inbred C57BL  Premedication
       Recombinant Proteins/ADMINISTRATION & DOSAGE/PHARMACOLOGY/  THERAPEUTIC
       USE  Spleen/CYTOLOGY  Support, Non-U.S. Gov't  Support, U.S. Gov't,
       P.H.S.  T-Lymphocytes/*DRUG EFFECTS/TRANSPLANTATION  Th2
       Cells/*CYTOLOGY/METABOLISM/TRANSPLANTATION  Tissue Donors  JOURNAL
       ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

