Loss of cytotoxic T‐lymphocyte antigen‐4 (CTLA‐4) at arthritis onset also breaks tolerance in autoreactive T cells. (a) Arthritis score (left) and incidence (right) of wild‐type (WT) MMC
+ or MMC
− and inducible knockout (iKO) MMC
+ mice that were CTLA‐4 depleted either on days 35, 36, 40 (iKO MMC
+ d35) or on days 49, 50, 54 (iKO MMC
+ d49). Kruskal–Wallis with Dunn's multiple comparison test for score; * depicts WT
+ versus iKO MMC
+ (d35) and Fisher's exact test for incidence; * depicts WT
+ versus iKO MMC+ (d35). (b) Interferon‐ γ (IFN‐γ) (left) and IL‐17 (right) T‐cell responses against unmodified (K264) or galactosylated (GalHy264) collagen type‐II (CII) peptides after deduction of the RPMI medium response, determined by ELISPOT from draining lymph node (dLN) cells on day 90 after immunization. Kruskal–Wallis with Dunn's multiple comparison. WT
+ versus both iKO
+ (c) Total anti‐CII antibody titres in serum of WT MMC
+ or MMC
− and iKO MMC
+ or MMC
− mice depleted day 35 or 49 post immunization. Kruskal–Wallis with Dunn's multiple comparison test. Error bars represent mean ± SEM. Differences were considered statistically significant with *P < 0·05.