OCA-B promotes autoimmune demyelination through control of stem-like CD4 + T cells.

Stem-like T cell populations can selectively contribute to autoimmunity, but the activities that promote and sustain these populations are incompletely understood. Here, we show that T cell-intrinsic loss of the transcription cofactor OCA-B protects mice from experimental autoimmune encephalomyelitis (EAE) while preserving responses to CNS infection. In adoptive transfer EAE models driven by multiple antigen encounters, OCA-B deletion nearly eliminates CNS infiltration, proinflammatory cytokine production and clinical disease. OCA-B-expressing CD4 ⁺ T cells within the CNS of mice with EAE comprise a minority of the population but display a memory phenotype and preferentially confer disease. In a relapsing-remitting EAE model, OCA-B T cell deficiency specifically protects mice from relapse. During remission, OCA-B promotes the expression of Tcf7 , Slamf6 , and Sell in proliferating T cell populations. At relapse, OCA-B loss results in both the accumulation of an immunomodulatory CD4 ⁺ T cell population expressing Ccr9 and Bach2 , and the loss of pro-inflammatory gene expression from Th17 cells. These results identify OCA-B as a driver of pathogenic stem-like T cells.