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 3

IL-10–secreting Tregs inhibit polyclonal T cell proliferative responses to anti-CD3 and cytokine production by allergen-stimulated Th2 cells.

This inhibition is reversed by an IL-10 antagonist. (A–F). Freshly isolated CFSE-labeled CD4⁺ T cells (CD4⁺ T-CFSE) were cultured with irradiated APCs and (A) medium or (B) anti-CD3. Alternatively, they were (C) cocultured at a ratio of 1 T_IL-4 to 4 CD4⁺ T-CFSE or (D–F) 1 IL-10–secreting Treg (IL-10–Treg) to 4 CD4⁺ T-CFSE. (E) Isotype control or (F) anti–IL-10 receptor monoclonal antibodies were added as indicated. Cell-cycle progression was analyzed at day 6. (G) Allergen-specific IL-10–secreting Tregs or Th2 cells were cultured alone or together (1 IL-10–secreting Treg to 4 Th2 cells) with APCs in medium or with cat allergen extract. Day 3 culture supernatants were analyzed by ELISA and cytometric bead array. Data are representative of 5 experiments. (H) Grass pollen allergen extract–stimulated cultures were established as above with the addition of a control isotype or anti–IL-10 receptor monoclonal antibody as indicated. Cytokine levels detected in the absence of allergen were 200 pg/ml or less and were subtracted in all groups. Data are representative of 3 experiments.