JCI - Reversing the defective induction of IL-10–secreting regulatory T cells in glucocorticoid-resistant asthma patients

Reversing the defective induction of IL-10–secreting regulatory T cells in glucocorticoid-resistant asthma patients

Emmanuel Xystrakis, Siddharth Kusumakar, Sandra Boswell, Emma Peek, Zoë Urry, David F. Richards, Tonye Adikibi, Carol Pridgeon, Margaret Dallman, Tuck-Kay Loke, Douglas S. Robinson, Franck J. Barrat, Anne O’Garra, Paul Lavender, Tak H. Lee, Christopher Corrigan, Catherine M. Hawrylowicz

Published in Volume 116, Issue 1

J Clin Invest. 2006; 116(1):146–155 doi:10.1172/JCI21759

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Figure 2

TGF-β is not upregulated by vitamin D3 and dexamethasone treatment and does not play a role in IL-10–secreting Treg–mediated suppression of Th1 and Th2 cytokine production.

(A) CD4⁺ T cells were stimulated for 7 days with (T vit/dex) or without (T neutral) vitamin D3 and dexamethasone, as for Figure 1, and restimulated without drugs for 48 hours. TGF-β and IL-10 levels in culture supernatants were determined by ELISA. Mean data of 3 experiments are shown. (B) CD4⁺ T cells were cultured for two 7-day cycles with or without vitamin D3 and dexamethasone and then activated with PMA and ionomycin for 4 hours. PBMCs were cultured without or with PMA and ionomycin for 4 hours. TGF-β and IL-10 mRNA were determined by real-time RT-PCR and expressed relative to unactivated PBMCs. A representative experiment of 4 is shown. (C) CD4⁺ T cell lines were cultured for 7 days with vitamin D3 and dexamethasone and then used in cocultures with fresh autologous T cells (1:4 ratio) and irradiated APCs. Day 3 supernatants were assessed for IFN-γ and IL-13 content. Mean data from 4 experiments is shown. *P < 0.05 using 2-tailed Student’s t test.