Low-dose interleukin-2 treatment selectively modulates CD4+ T cell subsets in patients with systemic lupus erythematosus

Abstract

Systemic lupus erythematosus (SLE) is a potentially life-threatening autoimmune disease characterized by altered balance of activity between effector and regulatory CD4+ T cells. The homeostasis of CD4+ T cell subsets is regulated by interleukin (IL)-2, and reduced production of IL-2 by T cells is observed in individuals with SLE. Here we report that treatment with low-dose recombinant human IL-2 selectively modulated the abundance of regulatory T (Treg) cells, follicular helper T (TFH) cells and IL-17-producing helper T (TH17) cells, but not TH1 or TH2 cells, accompanied by marked reductions of disease activity in patients with SLE.

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Figure 1: Immunological responses to low-dose rhIL-2.
Figure 2: Clinical responses to low-dose rhIL-2.

References

  1. 1

    Tsokos, G.C. N. Engl. J. Med. 365, 2110–2121 (2011).

  2. 2

    Liu, Z. & Davidson, A. Nat. Med. 18, 871–882 (2012).

  3. 3

    Crispín, J.C., Kyttaris, V.C., Terhorst, C. & Tsokos, G.C. Nat. Rev. Rheumatol. 6, 317–325 (2010).

  4. 4

    He, J. et al. Immunity 39, 770–781 (2013).

  5. 5

    Choi, J.Y. et al. Arthritis Rheumatol. 67, 988–999 (2015).

  6. 6

    Vincent, F.B., Northcott, M., Hoi, A., Mackay, F. & Morand, E.F. Arthritis Res. Ther. 15, R97 (2013).

  7. 7

    Yang, J. et al. Arthritis Rheum. 60, 1472–1483 (2009).

  8. 8

    Shin, M.S., Lee, N. & Kang, I. Curr. Opin. Rheumatol. 23, 444–448 (2011).

  9. 9

    Boyman, O. & Sprent, J. Nat. Rev. Immunol. 12, 180–190 (2012).

  10. 10

    Laurence, A. et al. Immunity 26, 371–381 (2007).

  11. 11

    Ballesteros-Tato, A. et al. Immunity 36, 847–856 (2012).

  12. 12

    Castela, E. et al. JAMA Dermatol. 150, 748–751 (2014).

  13. 13

    Hartemann, A. et al. Lancet Diabetes Endocrinol. 1, 295–305 (2013).

  14. 14

    Koreth, J. et al. N. Engl. J. Med. 365, 2055–2066 (2011).

  15. 15

    Klatzmann, D. & Abbas, A.K. Nat. Rev. Immunol. 15, 283–294 (2015).

  16. 16

    Saadoun, D. et al. N. Engl. J. Med. 365, 2067–2077 (2011).

  17. 17

    Humrich, J.Y. et al. Ann. Rheum. Dis. 74, 791–792 (2015).

  18. 18

    Matsuoka, K. et al. Sci. Transl. Med. 5, 179ra43 (2013).

  19. 19

    Lieberman, L.A. & Tsokos, G.C. J. Biomed. Biotechnol. 2010, 740619 (2010).

  20. 20

    Crispín, J.C. et al. J. Immunol. 181, 8761–8766 (2008).

  21. 21

    Hoes, J.N. et al. Ann. Rheum. Dis. 66, 1560–1567 (2007).

  22. 22

    Hochberg, M.C. Arthritis Rheum. 40, 1725 (1997).

  23. 23

    Petri, M. et al. N. Engl. J. Med. 353, 2550–2558 (2005).

  24. 24

    Furie, R.A. et al. Arthritis Rheum. 61, 1143–1151 (2009).

  25. 25

    Liu, W. et al. J. Exp. Med. 203, 1701–1711 (2006).

  26. 26

    Seddiki, N. et al. J. Exp. Med. 203, 1693–1700 (2006).

  27. 27

    Acosta-Rodriguez, E.V. et al. Nat. Immunol. 8, 639–646 (2007).

Download references

Acknowledgements

The work was supported by the National Sci-Tech Support Program (grant no. 2014BAI07B01; Z.L.), the National Basic Research Program of China 973 Program (grant no. 2014CB541903 (D.Y.), 2014CB541901 (N.S.) and 2010CB529104 (Z.L.)), the National Natural Science Foundation of China (NSFC) (grant no. 81373117 (J.H.), 31570880 (J.H.), 31530020 (Z.L.), 81429003 (D.Y.) and 81471601 (X.S.)), the Beijing Key Laboratory for Rheumatism and Immune Diagnosis (grant no. BZ0135; Z.L.), the Peking–Tsinghua Center for Life Sciences (Z.L.), the Priority Research Program of the Shandong Academy of Sciences (D.Y.), the Shandong Province Taishan Scholar Program (D.Y.) and the Australian National Health and Medical Research Council (NHMRC) Fellowship GNT1085509 (D.Y.).

Author information

J.H. and Xia Zhang participated in literature searches, study design, patient recruitment, data collection, data analysis, data interpretation and writing of the paper; Y.W., X.S., X.H., Z.H. and Y.C. analyzed the biological data; R.J., C.X., L.Z., J.F., Y.A., C.L., X.L., H. Ye, Y. Jia, L.R., R.L., S.C., Xuewu Zhang, Y.S., Y. Jin, H. Yao and Y.L. participated in patient recruitment and data collection; J.D., Y.G. and Y.A.L. participated in animal experiments; J.G., N.S. and E.F.M. participated in data interpretation and in writing the report; Z.L. and D.Y. participated in study design, data interpretation and writing of the paper; and all authors contributed to the critical revision of the manuscript and approved the final version.

Correspondence to Di Yu or Zhanguo Li.

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The authors declare no competing financial interests.

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He, J., Zhang, X., Wei, Y. et al. Low-dose interleukin-2 treatment selectively modulates CD4+ T cell subsets in patients with systemic lupus erythematosus. Nat Med 22, 991–993 (2016) doi:10.1038/nm.4148

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