Abstract
Chronic graft-versus-host disease (GVHD) occurs in recipients of allogeneic hematopoietic stem cell transplantation with a high frequency. Preclinical animal chronic GVHD models outlined in this chapter allow for the delineation of events that occur during chronic GVHD development. The DBA/2 → (C56BL/6 × DBA/2)F1 (BDF1) model is characterized by systemic lupus erythematosus (SLE)-like phenotype. The B10.D2 → Balb/c model presents many features of autoimmune scleroderma. The former model is useful in defining how alloreactive donor CD4+ T cells break B-cell tolerance, whereas the latter model is suitable for dissecting the pathogenesis of organ fibrosis. Our laboratory has demonstrated that injection of a single dose of strong CD137 agonists can prevent or cure chronic GVHD in these two models. In general, these models are particularly suited to screening the immunomodulatory therapeutics.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Blazar BR, Murphy WJ, Abedi M (2012) Advances in graft-versus-host disease biology and therapy. Nat Rev Immunol 12:443–458
Wolf D, von Lilienfeld-Toa M, Wolf AM, Schleuning M, von Bergwelt-Baildon M, Held SA et al (2012) Novel treatment concepts for graft-versus-host disease. Blood 119:16–25
Chu Y-W, Gress RE (2008) Murine models of chronic graft-versus-host disease: insights and unresolved issues. Biol Blood Marrow Transplant 14:365–378
Kim J, Choi WS, Kang H, Kim H-J, Suh J-H, Sakaguchi S et al (2006) Conversion of alloantigen-specific CD8+ T cell anergy to CD8+ T cell priming through in vivo ligation of glucocorticoid-induced TNF receptor. J Immunol 176:5223–5231
Kwon B (2010) Intervention with costimulatory pathway as a therapeutic approach for graft-versus-host disease. Exp Mol Med 42:675–683
Kim J, Park K, Kim HJ, Kim J, Kim HA, Jung D et al (2008) Breaking of CD8+ T cell tolerance through in vivo ligation of CD40 results in inhibition of chronic graft-versus-host disease and complete donor cell engraftment. J Immunol 181:7380–7389
Kaplan DH, Anderson BE, McNiff JM, Jain D, Schlomchik MJ, Shlomchik WD (2004) Target antigens determine graft-versus-host disease phenotype. J Immunol 173:5467–5475
Croft M (2009) The role of TNF superfamily members in T-cell function an diseases. Nat Rev Immunol 9:271–285
Lee SW, Park Y, Eun SY, Madireddi S, Cheroutre H, Croft M (2012) Cutting edge: 4-1BB controls regulatory activity in dendritic cells through promoting optimal expression of retinal dehydrogenase. J Immunol 189:2697–2701
Hsieh EH, Fernandez X, Wang J, Hamer M, Calvillo S, Croft M et al (2010) CD137 is required for M cell functional maturation but not lineage commitment. Am J Pathol 177:666–676
Choi BK, Kim YH, Kwon PM, Lee SC, Kang SW, Kim MS et al (2009) 4-1BB functions as a survival factor in dendritic cells. J Immunol 182:4107–4115
Kim HJ, Lee JS, Kim JD, Cha HJ, Kim A, Lee SK et al (2012) Reverse signaling through the costimulatory ligand CD137L in epithelial cells is essential for natural killer cell-mediated acute tissue inflammation. Proc Natl Acad Sci U S A 109:E13–E22
Blazar BR, Kwon BS, Panoskaltsis-Mortari A, Kwak KB, Peschon JJ, Taylor PA (2001) Ligation of 4-1BB (CDw137) regulates graft-versus-host disease, graft-versus-leukemia, and graft rejection in allogeneic bone marrow transplant recipients. J Immunol 166:3174–3183
Nozawa K, Ohata J, Sakurai J, Hashimoto H, Miyajima H, Yagita H et al (2001) Preferential blockade of CD8(+) T cell responses by administration of anti-CD137 ligand monoclonal antibody results in differential effect on development of murine acute and chronic graft-versus-host diseases. J Immunol 167:4981–4986
Via CS (2010) Advances in lupus stemming from the parent-into-F1 model. Trends Immunol 31:236–245
Kim J, Choi WS, La S, Suh JH, Kim BS, Cho HR et al (2005) Stimulation with 4-1BB (CD137) inhibits chronic graft-versus-host disease by inducing activation-induced cell death of donor CD4 T cells. Blood 105:2206–2213
Kim J, Kim HJ, Park K, Kim J, Choi HJ, Yagita H et al (2007) Costimulatory molecule-targeted immunotherapy of cutaneous graft-versus-host disease. Blood 110:776–782
Zhang C, Todorov I, Zhang Z, Liu Y, Kandeel F, Forman S et al (2008) Donor CD4+ T and B cells in transplants induce chronic graft-versus-host disease with autoimmune manifestations. Blood 107:2993–3001
Sakoda Y, Hashimoto D, Asakura S, Takeuchi K, Harada M, Tanimoto M et al (2007) Donor-derived thymic-dependent T cells cause chronic graft-versus-host disease. Blood 1009:1756–1764
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer Science+Business Media New York
About this protocol
Cite this protocol
Kim, J., Cho, H.R., Kwon, B. (2014). CD137 in Chronic Graft-Versus-Host Disease. In: Bayry, J. (eds) The TNF Superfamily. Methods in Molecular Biology, vol 1155. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-0669-7_9
Download citation
DOI: https://doi.org/10.1007/978-1-4939-0669-7_9
Published:
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-0668-0
Online ISBN: 978-1-4939-0669-7
eBook Packages: Springer Protocols