Accelerated thymocyte maturation in IL-12Rβ2-deficient mice contributes to increased susceptibility to autoimmune...

IL-12Rβ2(-/-) mice, which are unresponsive to IL-12, develop severe experimental autoimmune encephalomyelitis (EAE). The mechanisms for enhanced autoimmunity are incompletely understood. We report that in IL-12Rβ2(-/-) mice, thymocytes undergo markedly accelerated maturation. This occurs at the transition from a double positive (DP) to a single positive (SP) phenotype, resulting in higher numbers of CD4 and CD8 SP cells, and to a lesser extent at the transition from double negative (DN) to DP cells. Accelerated maturation is observed in mice injected with anti-CD3 to mimic pre-T-cell receptor stimulation, and also in mice immunized with myelin oligodendrocyte glycoprotein (MOG) peptide to induce EAE.