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Tob1 plays a critical role in the activation of encephalitogenic T cells in CNS autoimmunity

Ulf Schulze-Topphoff1, Simona Casazza, Michel Varrin-Doyer

  • 1Department of Neurology, University of California, San Francisco, CA 94143, USA.

The Journal of Experimental Medicine
|June 26, 2013
PubMed

Insights

The antiproliferative gene TOB1 plays a critical role in T cell responses driving experimental autoimmune encephalomyelitis (EAE). Low TOB1 expression in T cells may indicate a higher risk for multiple sclerosis progression.

Area of Science:

  • Immunology
  • Neuroscience
  • Genetics

Background:

  • Biomarkers for multiple sclerosis (MS) progression and treatment response are lacking.
  • Previous research linked low TOB1 gene expression in CD4+ T cells to increased MS risk after a first central nervous system (CNS) demyelinating event.

Purpose of the Study:

  • To investigate the role of the TOB1 gene in T cell-mediated autoimmune responses relevant to MS pathogenesis.
  • To explore TOB1 as a potential biomarker for demyelinating disease activity.

Main Methods:

  • Studied experimental autoimmune encephalomyelitis (EAE) in mice lacking the Tob1 gene (Tob1⁻/⁻).
  • Analyzed T cell infiltration, differentiation (Th1, Th17, Treg), and CNS inflammation in EAE models.
  • Utilized adoptive T cell transfer and cross-breeding strategies with transgenic mice (Rag1⁻/⁻, 2D2).

Main Results:

  • Tob1⁻/⁻ mice exhibited exacerbated EAE with increased CNS inflammation and T cell infiltration (CD4⁺, CD8⁺).
  • Reduced regulatory T cells and increased myelin-reactive Th1/Th17 cells were observed in Tob1⁻/⁻ mice.
  • Transfer of Tob1⁻/⁻ CD4⁺ T cells or crossing with 2D2 mice induced severe EAE, confirming Tob1's crucial role in T cell pathogenicity.

Conclusions:

  • Tob1 is essential for regulating adaptive T cell immunity involved in EAE development.
  • These findings support TOB1 as a potential biomarker for predicting and monitoring demyelinating disease activity in conditions like MS.

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