Low-dose IL-2 therapy invigorates CD8(+) T cells for viral control in systemic lupus erythematosus

Zhou, Pengcheng; Chen, Jiali; He, Jing; Zheng, Ting; Yunis, Joseph; Makota, Victor; Alexandre, Yannick O.; Gong, Fang; Zhang, Xia; Xie, Wuxiang; Li, Yuhui; Shao, Miao; Zhu, Yanshan; Sinclair, Jane E.; Miao, Miao; Chen, Yaping; Short, Kirsty R.; Mueller, Scott N.; Sun, Xiaolin; Yu, Di; Li, Zhanguo

Autoimmune diseases are often treated by glucocorticoids and immunosuppressive drugs that could increase the risk for infection, which in turn deteriorate disease and cause mortality. Low-dose IL-2 (Ld-IL2) therapy emerges as a new treatment for a wide range of autoimmune diseases. To examine its influence on infection, we retrospectively studied 665 patients with systemic lupus erythematosus (SLE) including about one third receiving Ld-IL2 therapy, where Ld-IL2 therapy was found beneficial in reducing the incidence of infections. In line with this clinical observation, IL-2 treatment accelerated viral clearance in mice infected with influenza A virus or lymphocytic choriomeningitis virus (LCMV). Noticeably, despite enhancing anti-viral immunity in LCMV infection, IL-2 treatment exacerbated CD8(+) T cell-mediated immunopathology. In summary, Ld-IL2 therapy reduced the risk of infections in SLE patients and enhanced the control of viral infection, but caution should be taken to avoid potential CD8(+) T cell-mediated immunopathology.