Agonistic Anti-CD137 Monoclonal Antibody Treatment Induces CD11bGr-1 Myeloid-derived Suppressor Cells.
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.
Lee
Jung-Mi
JM
Laboratory of Immunology, Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Korea.
Seo
Jeong-Hwan
JH
Kim
Yeon-Jeong
YJ
Kim
Yun-Sun
YS
Ko
Hyun-Jeong
HJ
Kang
Chang-Yuil
CY