From the Department of Immunology, Mayo Graduate and Medical Schools, Mayo Clinic, Rochester, MN; Cancer Center and Department of Pediatrics, Division of Bone Marrow Transplantation, University of Minnesota, Minneapolis; and Cardinal Bernardin Cancer Center, Loyola University Chicago, Maywood, IL.
T-cell anergy is a tolerance mechanism defined as a hyporesponsive status of antigen-specific T cells upon prior antigen encounter and is believed to play a critical role in the evasion of tumor immunity and the amelioration of allogeneic transplant rejection. Molecular mechanisms in controlling T-cell anergy are less known. We show here that administration of an agonistic monoclonal antibody (mAb) to CD137, a member of the tumor necrosis factor receptor superfamily, prevents the induction of CD8+ cytolytic T-lymphocyte (CTL) anergy by soluble antigens. More importantly, CD137 mAb restores the functions of established anergic CTLs upon reencountering their cognate antigen. As a result, infusion of CD137 mAb inhibits progressive tumor growth that is caused by soluble tumor antigen-induced tolerance in a P815R model. CD137 mAb also restores proliferation and effector functions of anergic alloreactive 2C T cells in a bone marrow transplantation model. Our results indicate that ligation of CD137 receptor delivers a regulatory signal for T-cell anergy and implicate manipulation of the CD137 pathway as a new approach to break T-cell tolerance.
Acute graft-versus-host disease in patients with Fanconi anemia or acquired aplastic anemia undergoing bone marrow transplantation from HLA-identical sibling donors: risk factors and influence on outc
Adult human hematopoietic cells provide functional hemangioblast activity
Annexin II mediates plasminogen-dependent matrix invasion by human monocytes: enhanced expression by macrophages
Antibody response to DBY minor histocompatibility antigen is induced after allogeneic stem cell transplantation and in healthy female donors
Bcl-xL antagonism of BCR-coupled mitochondrial phospholipase A2 signaling correlates with protection from apoptosis in WEHI-231 B cells
CCL16 activates an angiogenic program in vascular endothelial cells
Combined deficiency of protease-activated receptor-4 and fibrinogen recapitulates the hemostatic defect but not the embryonic lethality of prothrombin deficiency
Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray
Effects of prednisone and genetic polymorphisms on etoposide disposition in children with acute lymphoblastic leukemia
Enhanced in vivo platelet adhesion in vasodilator-stimulated phosphoprotein (VASP)–deficient mice