Amelioration of graft versus host disease by galectin-1.
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.
Baum
Linda G
LG
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Blackall
Douglas P
DP
Arias-Magallano
Sarah
S
Nanigian
Danielle
D
Uh
Soo Y
SY
Browne
Jordan M
JM
Hoffmann
Douglas
D
Emmanouilides
Christos E
CE
Territo
Mary C
MC
Baldwin
Gayle Cocita
GC
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
D000276:Adjuvants, Immunologic; D037483:Galectin 1; D007376:Interleukin-2; D015847:Interleukin-4; D007371:Interferon-gamma