Article thumbnail

Agonistic Anti-CD137 Monoclonal Antibody Treatment Induces CD11b+Gr-1+ Myeloid-derived Suppressor Cells

By Jung-Mi Lee, Jeong-Hwan Seo, Yeon-Jeong Kim, Yun-Sun Kim, Hyun-Jeong Ko and Chang-Yuil Kang


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-CD137 mAb 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

Topics: Brief Communication
Publisher: The Korean Association of Immunologists
OAI identifier:
Provided by: PubMed Central

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.

Suggested articles


  1. (2004). BS: 4-1BB-mediated immunotherapy of rheumatoid arthritis.
  2. (2006). BS: Dual immunoregulatory pathways of 4-1BB signaling.
  3. (2009). BS: Origins and funct i o n a l b a s i s o f r e g u l a t o r y
  4. CY: A humanized anti--4-1BB monoclonal antibody suppresses antigen-induced humoral immune response in nonhuman primates.
  5. (2002). DH: 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.
  6. (2004). 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;89-98,
  7. (2002). Fu YX: Administration of agonistic anti-4-1BB monoclonal antibody leads to the amelioration of experimental autoimmune encephalomyelitis.
  8. (2002). Fu YX: Costimulatory molecule-targeted antibody therapy of a spontaneous autoimmune disease. Nat Med 8;1405-1413,
  9. (2008). Identification of regulatory functions for 4-1BB and 4-1BBL in myelopoiesis and the development of dendritic cells.
  10. (2005). K w on BS, Kwon B: Stimulation with 4-1BB (CD137) inhibits chronic graft-versus-host disease by inducing activation-induced cell death of donor CD4+ T cells.
  11. (2010). Katsikis PD: In vivo stimulation of CD137 broadens primary antiviral CD8+ T cell responses.
  12. (2007). Melero I: Absence of surface expression of CD137 (4-1BB) on Myeloid-derived suppressor cells. Immunologia 26;121-126,
  13. (2009). Myeloid-derived suppressor cells a s r e g u l a t o r s o f t h e i m m u n e s y s t e m . N a t R e v I m m u n o l 9;162-174,
  14. (2007). S p e n c e r T , D i l l e h a y D , K w o n
  15. SH: 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.
  16. (2009). TH: Immune regulation by 4-1BB and 4-1BBL: complexities and challenges. Immunol Rev 229;192-215,