Using a mouse model to track the early immune response against an antigen conditionally expressed in the liver, we observed that liver CD4 T cells targeting this antigen acquired an immuno-exhausted (TIGIT, PRDM1, CTLA-4) transcriptomic signature comparable to that of circulating liver-autoreactive CD4 T cells in AILD patients, and are essential for inducing a complete immune response against a liver antigen responsible for liver damage. Here, CD4 is linked to angioimmunoblastic T-cell lymphoma.