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

• Published in: Blood 1995-12, Vol.86 (12), p.4422-4429
• Main Authors: Pan, Luying, Jr, John Delmonte, Jalonen, Candice K., Ferrara, James L.M.
• Format: Article
• Language: English
• Subjects: Acute Disease; AIDS/HIV; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Biological and medical sciences; Bone Marrow Transplantation - adverse effects; Bone marrow, stem cells transplantation. Graft versus host reaction; Cell Differentiation - drug effects; Female; Graft vs Host Disease - etiology; Graft vs Host Disease - prevention & control; Granulocyte Colony-Stimulating Factor - administration & dosage; Granulocyte Colony-Stimulating Factor - pharmacology; Granulocyte Colony-Stimulating Factor - therapeutic use; Hematopoietic Stem Cell Transplantation - adverse effects; Humans; Immunologic Factors - administration & dosage; Immunologic Factors - pharmacology; Immunologic Factors - therapeutic use; Interleukin-4 - biosynthesis; Lymphocyte Activation; Medical sciences; Mice; Mice, Inbred C57BL; Premedication; Recombinant Proteins - administration & dosage; Recombinant Proteins - pharmacology; Recombinant Proteins - therapeutic use; Spleen - cytology; T-Lymphocytes - drug effects; T-Lymphocytes - transplantation; Th2 Cells - cytology; Th2 Cells - metabolism; Th2 Cells - transplantation; Tissue Donors; Transfusions. Complications. Transfusion reactions. Cell and gene therapy
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V86.12.4422.bloodjournal86124422

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-γ) 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-γ 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-γ 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.