Autoreactive memory Th17 cells are principally derived from T-bet+RORγt+ Th17/1 effectors.

Effector Th17 cells, including IFN-γ-IL-17+ (eTh17) and IFN-γ+IL-17+ (eTh17/1) subsets, play critical pathogenic functions in the induction of autoimmunity. As acute inflammation subsides, a small proportion of the effectors survive and convert to memory Th17 cells (mTh17), which sustain chronic inflammation in autoimmune diseases. Herein, we investigated the differential contributions of eTh17 versus eTh17/1 to the memory pool using an experimental model of ocular autoimmune disease. Our results show that adoptive transfer of Tbx21-/- CD4+ T cells or conditional deletion of Tbx21 in Th17 cells leads to diminished eTh17/1 in acute phase and functionally compromised mTh17 in chronic phase. Further, adoptive transfer of disease-specific eTh17/1, but not eTh17, leads to generation of mTh17 and sustained ocular inflammation. Collectively, our data demonstrate that T-bet-dependent eTh17/1 cells generated during the acute inflammation are the principal effector precursors of pathogenic mTh17 cells that sustain the chronicity of autoimmune inflammation.