LEF1 and niche factors determine T cell stemness across chronic diseases.

LEF1+ TCF1 high T cells define a true self-renewing T cell stemness pool in chronic diseases, with LEF1 being essential for this capacity.

• Why it matters: Understanding the regulation of T cell stemness is crucial for addressing persistent immune responses in autoimmunity and chronic infections, where T cell exhaustion hampers immune control.
• What they did: Using preclinical models of autoimmune type 1 diabetes and chronic infection, the study identified a subset of TCF1 high T cells expressing LEF1, which form a self-renewing T stem cell pool and give rise to progenitor and terminally differentiated T cells, with LEF1 being necessary for stemness.
• The result: Targeting niche signals like integrins or Notch impairs T cell stemness and prevents disease, highlighting LEF1 and niche factors as key regulators of T cell persistence across chronic conditions.