Stimulation with 4-1BB (CD137) inhibits chronic graft-versus-host disease by inducing activation-induced cell death of donor CD4+ T cells
| Autor: | Byungsuk Kwon, Juyang Kim, Soojin La, Byoung S. Kwon, Byoung-Sam Kim, Hong R. Cho, Woon S. Choi, Jae-Hee Suh |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
CD4-Positive T-Lymphocytes
medicine.medical_treatment Immunology Graft vs Host Disease Mice Inbred Strains Receptors Nerve Growth Factor Biology Biochemistry Receptors Tumor Necrosis Factor Mice Tumor Necrosis Factor Receptor Superfamily Member 9 Antigens CD immune system diseases medicine Animals Transplantation Homologous Autoantibodies B-Lymphocytes Cell Death CD137 Autoantibody Antibodies Monoclonal Cell Biology Hematology T lymphocyte Immunotherapy medicine.disease Graft-versus-host disease Antibody Formation Chronic Disease Female Tumor necrosis factor alpha Stem cell CD8 |
| Zdroj: | Blood. 105:2206-2213 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood-2004-06-2080 |
| Popis: | 4-1BB, a member of the tumor necrosis factor (TNF) receptor superfamily, is a costimulator for activated T cells. Previous studies have established that treatment with agonistic anti–4-BB monoclonal antibody (3H3) is effective in reversing the progression of spontaneous systemic lupus erythematosus. Its therapeutic effect is mediated by suppression of autoantibody production. In this report, we show that a single injection of 3H3 blocks chronic graft-versus-host disease (cGVHD) in the parent-into-F1 model. In particular, donor CD4+ T cells are rapidly eliminated from host spleens by activation-induced cell death after 4-1BB triggering. Since donor CD4+ T cells are required for the development of cGVHD, and 3H3-mediated inhibition of autoantibody production occurs without donor CD8+ T cells, 3H3 blocks cGVHD by preventing alloreactive donor CD4+ T cells from activating host B cells. Importantly, 3H3 treatment can reverse the progression of advanced cGVHD. Our findings indicate that agonistic anti–4-1BB monoclonal antibody has potential as an immunotherapeutic agent for preventing and treating cGVHD. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|