Colonic Treg TCRs (CT2 and CT6) drive Teff cell development in inflammation. Colonic Treg TCRs (CT2 and CT6) drive Teff cell development in inflammation.

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Volume 17, Issue 1, Pages (September 2016)
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Colonic Treg TCRs (CT2 and CT6) drive Teff cell development in inflammation. Colonic Treg TCRs (CT2 and CT6) drive Teff cell development in inflammation. (A) Experimental model. Four- to 5-week-old CD45.1 specific pathogen–free (SPF) mice were administered αIL10R (1 mg per mouse) on day 0 and kept on 1% DSS water for 7 days to initiate colitis. Control mice were given isotype IgG (1 mg per mouse) on day 0. Four days after initiation of colitis, congenically marked naïve CT2/CT6 Tg cells (105) were intravenously transferred and analyzed 7 days later. (B to D) Effector cell induction and expansion with colitis. Transferred TCR Tg cells from the colon lamina propria (cLP) were analyzed by flow cytometry for (B) the development of Teff (CD44hi CD62Llo Foxp3−) and Treg (Foxp3+) markers (P = 0.000003, P = 0.0007, P = 0.0024, P = 0.0157, Student’s t test; n = 10), (C) up-regulation of cytokines using IL-17AGFP and IFNγYFP (P = 0.000001, P = 0.0007, P = 0.0029, Student’s t test; n = 10 for CT2 and 7 for CT6), (D) proliferation indicated by CTV dilution (P = 0.000002, P = 0.00002, Student’s t test; n = 10 for CT2 and 7 and 8 for CT6), and (E) expansion indicated by the in vivo frequency among the host CD4+ T cells (P = 0.00005, P = 0.0275, Student’s t test; n = 10 for CT2 and 10 and 11 for CT6). Bars indicate mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. ns, not significant. Jiani N. Chai et al. Sci. Immunol. 2017;2:eaal5068 Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works