Agonistic Anti-CD137 Monoclonal Antibody Treatment Induces CD11bGr-1 Myeloid-derived Suppressor Cells

Immune Netw. 2010 Jun;10(3):104-8. doi: 10.4110/in.2010.10.3.104. Epub 2010 Jun 30.

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-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.

Keywords: CD11b+Gr-1+ cells; CD137; Immunosuppression; Myeloid-derived suppressor cells.