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

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.

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