title: Amelioration of graft versus host disease by galectin-1.
abstract: Graft versus host disease is a significant cause of morbidity and mortality following allogeneic hematopoietic stem cell transplantation. Galectin-1, a mammalian lectin that modulates T cell function and apoptosis, has been shown to be immunomodulatory in animal models of autoimmune disease. We investigated the efficacy of galectin-1 in a murine model of graft versus host disease and found that 68% of galectin-1-treated mice survived, compared to 3% of vehicle-treated mice. Galectin-1-treated animals also had reduced inflammatory infiltrates in tissues compared to animals treated with vehicle alone. Galectin-1 did not affect engraftment of donor hematopoietic cells. However, galectin-1-treated animals demonstrated increased cellularity in bone marrow and spleen with increased numbers of splenic B cells and CD4 T cells compared to those animals treated with vehicle alone. Galectin-1 treatment also significantly improved reconstitution of normal splenic architecture following transplant. Production of type I cytokines interleukin-2 (IL-2) and interferon-gamma was reduced in splenocytes derived from galectin-1-treated transplanted mice when compared to animals treated with vehicle alone, while production of the type II cytokines, IL-4 and IL-10, was similar between the two groups of animals. Although splenocytes from galectin-1-treated transplanted animals responded to both third party antigens and leukemic challenge, host alloreactivity was significantly reduced when compared to cells from vehicle-treated animals. These results demonstrate that galectin-1 therapy is capable of increasing survival and suppressing the graft versus host immune response without compromising engraftment or immune reconstitution following allogeneic hematopoietic stem cell transplant.
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
authors.forename: Linda G
authors.initials: LG
authors.lastname: Baum
authors.forename: Douglas P
authors.initials: DP
authors.lastname: Blackall
authors.forename: Sarah
authors.initials: S
authors.lastname: Arias-Magallano
authors.forename: Danielle
authors.initials: D
authors.lastname: Nanigian
authors.forename: Soo Y
authors.initials: SY
authors.lastname: Uh
authors.forename: Jordan M
authors.initials: JM
authors.lastname: Browne
authors.forename: Douglas
authors.initials: D
authors.lastname: Hoffmann
authors.forename: Christos E
authors.initials: CE
authors.lastname: Emmanouilides
authors.forename: Mary C
authors.initials: MC
authors.lastname: Territo
authors.forename: Gayle Cocita
authors.initials: GC
authors.lastname: Baldwin
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000276:immunology; D016026:Bone Marrow Transplantation / Q000276:immunology* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D037483:Galectin 1 / Q000494:pharmacology*; D006086:Graft vs Host Disease / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D006410:Hematopoiesis / Q000187:drug effects / Q000276:immunology; D006651:Histocytochemistry; D007371:Interferon-gamma / Q000096:biosynthesis / Q000097:blood; D007376:Interleukin-2 / Q000096:biosynthesis / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008806:Mice, Inbred AKR; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D037483:Galectin 1; D007376:Interleukin-2; D015847:Interleukin-4; D007371:Interferon-gamma