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

Author:

Zhou PengchengORCID,Chen Jiali,He Jing,Zheng Ting,Yunis JosephORCID,Makota Victor,Alexandre Yannick O.,Gong FangORCID,Zhang Xia,Xie WuxiangORCID,Li Yuhui,Shao Miao,Zhu Yanshan,Sinclair Jane E.,Miao Miao,Chen YapingORCID,Short Kirsty R.,Mueller Scott N.ORCID,Sun Xiaolin,Yu Di,Li ZhanguoORCID

Abstract

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.

Funder

National Key Research and Development Program of China

National Natural Science Foundation of China

Peking-Tsinghua Center for Life Sciences

Australian National Health and Medical Research Council Project

Bellberry-Viertel Senior Medical Research fellowship

Beijing sci-Tech Program

Clinical Medicine Plus X-Young scholars Project of Peking University

Publisher

Public Library of Science (PLoS)

Subject

Virology,Genetics,Molecular Biology,Immunology,Microbiology,Parasitology

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