Atypical EAE in α4^−/− mice and predominant cerebral T cell infiltration are inhibited by administration of blocking antibodies to CD11a (αL integrin). EAE was induced in wild-type and T cell conditional α4^−/− mice by immunization with MOG_35-55 plus CFA. (A) Relative expression of α4 integrin and CD11a (αL integrin) in CD4⁺ T cells isolated from the brain of untreated wild-type or α4^−/− EAE mice (means + SD, n = 3). (B) Naive wild-type T cells were cultured under Th1 or Th17 polarizing conditions. On day 4, intracellular cytokine staining and surface staining for CD11a (tinted histogram, isotype control; black line, anti-CD11a expression) were performed. Shown are representatives of two independent experiments. (C and D) Starting from day 5 after induction of EAE in wild-type and α4^−/− mice, control rat IgG or antibodies to CD11a were administered i.p. every other day until the development of clinical signs of disease. (C) Means of clinical scores + SEM are depicted according to the classical EAE score (n = 6). The rat IgG control-treated and anti-CD11a–treated α4^−/− groups were compared with two-way ANOVA and Bonferroni’s post-testing. (D) Treatment effect of anti-CD11a in α4^−/− mice according to the ataxia score (mean + SEM, n = 4). The two groups were compared with two-way ANOVA and Bonferroni’s post-testing. (E and F) Absolute numbers of brain-infiltrating T cells isolated at the peak of disease from wild-type (E) and α4^−/− mice (F) without or with anti-CD11a treatment (means + SD of absolute CD4⁺ T cell numbers, n = 6, Student’s t test).