Pharmacodynamics of regulatory T cells in mice and humans treated with low-dose IL-2 Guillaume Churlaud, PharmD, PhD, Chadi Abbara, PharmD, PhD, Pierre-Axel.

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Pharmacodynamics of regulatory T cells in mice and humans treated with low-dose IL-2 Guillaume Churlaud, PharmD, PhD, Chadi Abbara, PharmD, PhD, Pierre-Axel Vinot, MSc, Gwladys Fourcade, PhD, Paul-Gydeon Ritvo, PhD, Roberta Lorenzon, MD, Michelle Rosenzwajg, MD, PhD, Bertrand Diquet, PharmD, PhD, David Klatzmann, MD, PhD Journal of Allergy and Clinical Immunology Volume 142, Issue 4, Pages 1344-1346.e3 (October 2018) DOI: 10.1016/j.jaci.2018.06.006 Copyright © 2018 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Dynamics and modeling of Treg cells in mice treated with IL2. A, Dynamics of Treg cells in blood during a 5-day course of IL-2 (pool of 3 different experiments; n = 10). Observed and in silico modeling of Treg-cell dynamics in blood (B) after a 5-day course of daily injections of 50,000 IU of IL-2, and (C) followed by reinjections of 50,000 IU of IL-2 every 3 days. Journal of Allergy and Clinical Immunology 2018 142, 1344-1346.e3DOI: (10.1016/j.jaci.2018.06.006) Copyright © 2018 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Dynamics and modeling of CD4+ Treg cells in humans after ld-IL2. A, Observed Treg-cell dynamics in humans after a 5-day course of ld-IL2 (doses ranging from 0.33 MIU/d to 3 MIU/d) (n = 6 patients/treatment). B, Comparison of in silico modeling and real Treg-cell dynamics (n = 40) after reinjections of 1 MIU of IL-2 every 15 days after a 5-day course of IL-2. Journal of Allergy and Clinical Immunology 2018 142, 1344-1346.e3DOI: (10.1016/j.jaci.2018.06.006) Copyright © 2018 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 Dynamics and modeling of Treg cells in mice treated with IL2. Results are expressed as relative variation compared with the PBS-treated group. These data are from a pool of 3 different experiments (n = 10) using C57BL/6 mice. Treg-cell dynamics in blood at 2 and 24 hours postinjection (A) and Treg-cell dynamics in blood and spleen at 2 hours postinjection (B), during a 5-day course of 50,000 IU/d of IL-2. C, Dynamics of Treg cells in blood during a 5-day course of 50,000 IU of IL-2 and then reinjection every 3, 7, or 15 days with 50,000 IU of IL-2. Comparison between IL-2 and PBS groups was done using the Mann-Whitney test (*P ≤ .05; **P ≤ .01; ***P ≤ .0001). Journal of Allergy and Clinical Immunology 2018 142, 1344-1346.e3DOI: (10.1016/j.jaci.2018.06.006) Copyright © 2018 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 Dynamics and modeling of CD4+ Treg cells in humans after ld-IL2. A and B, Vertical dotted lines represent IL-2 injection. Blood sampling was performed just before IL-2 injection. Results are expressed as delta variation of Treg-cell frequency in CD4+ T cells, that is, % of Treg cells in CD4+ of the day minus % of Treg cells in CD4+ at day 0. Fig E2, A, Modeling of the results obtained in humans after a 5-day course of ld-IL2 (doses ranging from 0.33 MIU/d to 3 MIU/d). Fig E2, B, In silico modeling of Treg-cell dynamics after injections of ld-IL2 every 3 or 15 days after a 5-day course of ld-IL2, using 0.33, 1, or 3 MIU/injection. Journal of Allergy and Clinical Immunology 2018 142, 1344-1346.e3DOI: (10.1016/j.jaci.2018.06.006) Copyright © 2018 American Academy of Allergy, Asthma & Immunology Terms and Conditions