β₂AR-mediated signals attenuate T cell–mediated inflammation. (A) WT mice were immunized with MOG_35-55 peptide and scored for clinical signs of EAE. Saline (n = 7) or clenbuterol (0.4 mg/kg/day, n = 7) was injected i.v. for 3 consecutive days at the disease onset. (B) EAE was induced in Adrb2^+/− (n = 10) and Adrb2^−/− (n = 12) mice. (C) Adrb2^+/− and Adrb2^−/− mice were treated with saline or clenbuterol (0.4 mg/kg/day) at the onset of EAE (at least six mice per group). Clinical scores are shown as mean + SEM. The days of drug treatment are indicated by arrows (A and C). (D) 7 d after immunization with OVA protein, WT mice received continuous 3-d administration of saline (n = 5) or clenbuterol (40 mg/kg/day, n = 5), and were challenged with OVA in the ear. DTH responses were assessed by ear swelling at the indicated times. (E) OVA-induced DTH responses were measured in Adrb2^+/− (n = 8) and Adrb2^−/− (n = 8) mice as in D. (F) DTH was induced in Adrb2^+/− and Adrb2^−/− mice during administration of saline or clenbuterol (40 mg/kg/d, five mice per group) and measured as in D. Ear swelling is shown as mean + SEM (D–F). (G and H) Frequencies (top) and numbers (bottom) of Th17 (CD3⁺CD4⁺IL-17⁺IFN-γ⁻) and/or Th1 (CD3⁺CD4⁺IFN-γ⁺IL-17⁻) cells were analyzed in the draining inguinal LNs of Adrb2^+/− (+/−) and Adrb2^−/− (−/−) mice 14 d after immunization with MOG_35-55 peptide (G) or 7 d after immunization with OVA (H). The dashed lines show the background levels in the inguinal LNs of unimmunized WT mice. Each symbol represents an individual mouse and bars indicate means (G and H). Data are representative of four (A) or two (C, D, and F) experiments, or pooled from two experiments (B, E, G, and H). Sal, saline; Clen, clenbuterol. *, P < 0.05; **, P < 0.01; ***, P < 0.001; ns, not significant. P-values were obtained by Mann-Whitney U test (A–C) or unpaired Student’s t test (D–H).