Figure 6.

T_reg cells generated from anergic CD4⁺ polyclonal T cells prevent arthritis and colitis. (a–c) Lymphopenic Tcra^−/− B6G7F1 mice were reconstituted with 1.5 × 10⁶ sorted syngeneic Teff/mem, anergic, or T_reg cell CD4⁺ polyclonal T cells from a Foxp3^DTR mouse for a period of 21 d. On day 21, 10⁴ naive KRN transgenic CD4⁺ T cells were transferred into these mice (as well as into control WT and Tcra^−/− B6G7F1 hosts) and then recipients were monitored over 12 d for arthritis development as described⁹, with the (a) number of KRN cells recovered, and (b) clinical arthritis index score on day 12 after KRN cell transfer as indicated. (c) CD73 and FR4 expression on KRN T cells on day 33. (d–f) A total of 2 × 10⁵ congenic–marked naive polyclonal CD4⁺ T cells were adoptively transferred into Tcra^−/− B6 mice either alone or in combination with 4 × 10⁵ Teff/mem, anergic, or T_reg cell CD4⁺ polyclonal cells sorted from Foxp3^GFP mice, and then recipients were monitored over 8 weeks for weight loss. (d) Number of donor naive cells recovered at the end of week 8. (e) Change in body weight of Tcra^−/− B6 mice receiving naive cells alone, or naive plus Teff/mem, anergic or T_reg cells. (f) Representative H&E staining of the colon (all panels same magnification, 200µm). Mean data shown are representative of 3 (a–c) or 2 (d–f) independent experiments, with n = 2 to 3 mice per group. Error bars represent the SEM. (a–c, d). Cells pooled from spleen and lymph nodes (inguinal, axillary, brachial, cervical, mesenteric and pancreatic). One-way ANOVA; * p < 0.05, ** p < 0.01, *** p < 0.001 **** p < 0.0001, non-significant (ns). Points denote individual mice.