Accelerated thymocyte maturation in IL-12Rβ2-deficient mice contributes to increased susceptibility to autoimmune inflammatory demyelination.
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.
Gran
B
B
Department of Neurology, Thomas Jefferson University, 300 JHN Building, 900 Walnut Street, Philadelphia, PA 19107, USA. bruno.gran@nottingham.ac.uk
Yu
S
S
Zhang
G X
GX
Rostami
A
A
D000818:Animals; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D004198:Disease Susceptibility; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics* / Q000276:immunology*; D005260:Female; D018664:Interleukin-12 / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000494:pharmacology; D063308:Myelin-Oligodendrocyte Glycoprotein; D013950:Thymus Gland / Q000276:immunology
D017252:CD3 Complex; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D018664:Interleukin-12