Interleukin-7 is required for CD4+ T cell activation and autoimmune neuroinflammation

- Optimal activation CD4+ T cells both in vitro and in vivo was found to require IL-7.
- IL-7 signaling pathways intersect and synergize with the TCR to promote activation.
- IL-7Rα blockade preferentially induced apoptosis in recently engaged CD4+ T cells.
- Anti-IL-7Rα inhibited induction, progression and relapses of EAE, a model of MS.
- Findings should be widely applicable to CD4+ T cell-mediated responses and diseases.

IL-7 is known to be vital for T cell homeostasis but has previously been presumed to be dispensable for TCR-induced activation. Here, we show that IL-7 is critical for the initial activation of CD4+ T cells in that it provides some of the necessary early signaling components, such as activated STAT5 and Akt. Accordingly, short-term in vivo IL-7Rα blockade inhibited the activation and expansion of autoantigen-specific CD4+ T cells and, when used to treat experimental autoimmune encephalomyelitis (EAE), prevented and ameliorated disease. Our studies demonstrate that IL-7 signaling is a prerequisite for optimal CD4+ T cell activation and that IL-7R antagonism may be effective in treating CD4+ T cell-mediated neuroinflammation and other autoimmune inflammatory conditions.