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The rise of IL-2 therapy — a picture beyond Treg cells

Nature Reviews Rheumatology volume 13, page 386 (2017)Cite this article

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We thank Dr Jens Y. Humrich and Dr Gabriela Riemekasten for their interest in our study1, which they discussed in a News & Views commentary (Humrich, J. Y. & Riemekasten, G. The rise of IL-2 therapy — a novel biologic treatment for SLE. Nat. Rev. Rheumatol. 12, 695-696; 2016)2. We are particularly excited that more clinical and basic scientists are working to understand the mechanisms of action underpinning the promising 'experimental medicine' observations of low-dose IL-2 therapy in systemic lupus erythematosus (SLE). After reading the commentary, however, we noted that there was a misunderstanding of the research design of our study. We hereby provide further clarification.

The inspiration for this study of low-dose IL-2 therapy in autoimmune diseases came from our previous publication showing that hyperactivation of follicular helper T (TFH) cells correlated with disease activity in patients with SLE and rheumatoid arthritis3; this is a different focus from the studies of low-dose IL-2 therapy, which centred on regulatory T (Treg) cells4,5,6. Although IL-2 had been shown to suppress TFH and type 17 T helper (TH17) cells in mouse models7,8, its effects in human cells were unknown. We started our study in 2013, with clinical responses as the primary end point and an emphasis on immunological responses, including changes in TFH, TH17 and Treg cells, as secondary end points9. For the first time, we demonstrated that low-dose IL-2 therapy could suppress TFH and TH17 cells in humans1. In addition, using a mouse model, we revealed that suppression of TFH and TH17 cells was as sensitive to low-dose IL-2 as the promotion of Treg cells. During the peer review process, we were asked to exclude the possibility that the increase in Treg cells and decreases in TFH and TH17 cells accompanying low-dose IL-2 administration were a consequence of significantly lowered disease activity. Therefore, we analysed the immunological phenotype in another, separate cohort of patients who underwent a comparable response under conventional immunosuppressive treatments, and found no such changes in Treg, TFH and TH17 cells. This separate cohort was not a placebo-control group and we agree with the proposal of Drs Humrich and Riemekasten that a parallel study would be ideal.

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Authors and Affiliations

  1. Department of Rheumatology and Immunology, Peking University People's Hospital, 11 Xizhimen South Street, 100044, Beijing, China

    Zhanguo Li & Jing He

  2. Department of Immunology and Infectious Disease, John Curtin School of Medical Research, Australian National University, Canberra, 0200, ACT, Australia

    Di Yu

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  1. Zhanguo Li
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Correspondence to Zhanguo Li or Di Yu.

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Li, Z., He, J. & Yu, D. The rise of IL-2 therapy — a picture beyond Treg cells. Nat Rev Rheumatol 13, 386 (2017). https://doi.org/10.1038/nrrheum.2017.70

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