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

PLoS Pathog. 2021 Oct 7;17(10):e1009858. doi: 10.1371/journal.ppat.1009858. eCollection 2021 Oct.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology*
  • Cohort Studies
  • Female
  • Humans
  • Immunocompromised Host / immunology
  • Immunosuppressive Agents / pharmacology*
  • Interleukin-2 / pharmacology*
  • Lupus Erythematosus, Systemic / immunology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Opportunistic Infections / immunology*
  • Retrospective Studies

Substances

  • Immunosuppressive Agents
  • Interleukin-2

Grants and funding

This study was supported by the National Key Research and Development Program of China (2017YFC0909003 to D.Y.); National Natural Science Foundation of China (NSFC) grants 31530020, 91742115 (to Z.L.), 82071813 (to J.H.), 81970759 (to T.Z.) and 81971520 (to X. S.), Peking-Tsinghua Center for Life Sciences (to Z.L.). Australian National Health and Medical Research Council (NHMRC) project GNT1147709, and the Bellberry-Viertel Senior Medical Research fellowship (to D.Y.). Beijing sci-Tech Program (Z191100006619114 to J.H.) and Clinical Medicine Plus X-Young scholars Project of Peking University (PKU2020LCXQ018 to J.H.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.