Agonistic Anti-CD137 Monoclonal Antibody Treatment Induces CD11b+Gr-1+ Myeloid-derived Suppressor Cells
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초록
CD137 (4-1BB/tnfrsf9) has been shown to co-stimulate T cells. However, agonistic anti-CD137 monoclonal antibody (mAb) treatment can suppress CD4+ T cells, ameliorating autoimmune diseases, whereas it induces activation of CD8+ T cells, resulting in diverse therapeutic activity in cancer,viral infection. To investigate the CD137-mediated T cell suppression mechanism, we examined whether anti-CD137mAb treatment could affect CD11b+Gr-1+ myeloid-derived suppressor cells (MDSCs). Intriguingly, anti-CD137 mAb injection significantly increased CD11b+Gr-1+ cells, peaking at days 5 to 10 and continuing for at least 25 days. Furthermore, this cell population could suppress both CD8+T cells and CD4+ T cells. Thus, this study demonstrated that,for the first time, anti-CD137 mAb treatment could induce CD11b+Gr-1+ MDSCs under normal conditions, suggesting a possible relationship between myeloid cell induction and CD137-mediated immune suppression.
Abstract
CD137 (4-1BB/tnfrsf9) has been shown to co-stimulate T cells. However, agonistic anti-CD137 monoclonal antibody (mAb) treatment can suppress CD4+ T cells, ameliorating autoimmune diseases, whereas it induces activation of CD8+ T cells, resulting in diverse therapeutic activity in cancer,viral infection. To investigate the CD137-mediated T cell suppression mechanism, we examined whether anti-CD137mAb treatment could affect CD11b+Gr-1+ myeloid-derived suppressor cells (MDSCs). Intriguingly, anti-CD137 mAb injection significantly increased CD11b+Gr-1+ cells, peaking at days 5 to 10 and continuing for at least 25 days. Furthermore, this cell population could suppress both CD8+T cells and CD4+ T cells. Thus, this study demonstrated that,for the first time, anti-CD137 mAb treatment could induce CD11b+Gr-1+ MDSCs under normal conditions, suggesting a possible relationship between myeloid cell induction and CD137-mediated immune suppression.
참고문헌 (18)
- Vinay DS, "Dual immunoregulatory pathways of 4-1BB signaling", J Mol Med, 84, pp.726~736 (2006)
- Miller RE, "4-1BB-specific monoclonal antibody promotes the generation of tumor-specific immune responses by direct activation of CD8 T cells in a CD40-dependent manner", J Immunol, 169, pp.1792~1800 (2002)
- Xu D, "NK and CD8+ T cell-mediated eradication of poorly immunogenic B16-F10 melanoma by the combined action of IL-12 gene therapy and 4-1BB costimulation", Int J Cancer, 109, pp.499~506 (2004)
- Halstead ES, "In vivo stimulation of CD137 broadens primary antiviral CD8+ T cell responses", Nat Immunol, 3, pp.536~541 (2002)
- Hong HJ, "A humanized anti--4-1BB monoclonal antibody suppresses antigen-induced humoral immune response in nonhuman primates", J Immunother, 23, pp.613~621 (2000)
- Sun Y, "Costimulatory molecule-targeted antibody therapy of a spontaneous autoimmune disease", Nat Med, 8, pp.1405~1413 (2002)
- Sun Y, "Administration of agonistic anti-4-1BB monoclonal antibody leads to the amelioration of experimental autoimmune encephalomyelitis", J Immunol, 168, pp.1457~1465 (2002)
- Foell J, "CD137 costimulatory T cell receptor engagement reverses acute disease in lupus-prone NZB x NZW F1 mice", J Clin Invest, 111, pp.1505~1518 (2003)
- Seo SK, "4-1BB-mediated immunotherapy of rheumatoid arthritis", Nat Med, 10, pp.1088~1094 (2004)
- Foell JL, "Engagement of the CD137 (4-1BB) costimulatory molecule inhibits and reverses the autoimmune process in collagen-induced arthritis and establishes lasting disease resistance", Immunology, 113, pp.89~98 (2004)
- Kim J, "Stimulation with 4-1BB (CD137) inhibits chronic graft-versus-host disease by inducing activation-induced cell death of donor CD4+ T cells", Blood, 105, pp.2206~2213 (2005)
- Kim YH, "4-1BB costimulation enhances HSV-1-specific CD8+ T cell responses by the induction of CD11c+CD8+T cells", Cell Immunol, 238, pp.76~86 (2005)
- Vinay DS, "Origins and functional basis of regulatory CD11c+CD8+ T cells", Eur J Immunol, 39, pp.1552~1563 (2009)
- Lee SW, "Identification of regulatory functions for 4-1BB and 4-1BBL in myelopoiesis and the development of dendritic cells", Nat Immunol, 9, pp.917~926 (2008)
- Niu L, "Cytokine-mediated disruption of lymphocyte trafficking, hemopoiesis, and induction of lymphopenia, anemia, and thrombocytopenia in anti-CD137-treated mice", J Immunol, 178, pp.4194~4213 (2007)
- Gabrilovich DI, "Myeloid-derived suppressor cells as regulators of the immune system", Nat Rev Immunol, 9, pp.162~174 (2009)
- Dubrot J, "Absence of surface expression of CD137 (4-1BB) on Myeloid-derived suppressor cells", Immunologia, 26, pp.121~126 (2007)
- Wang C, "Immune regulation by 4-1BB and 4-1BBL: complexities and challenges", Immunol Rev, 229, pp.192~215 (2009)
