Using tissue-based spatial transcriptomics and proteomics, we identified upregulation of the immune checkpoint protein, cytotoxic T lymphocyte–associated protein 4 (CTLA4), on CD8+ T cells adjacent to regions of active fibrogenesis in human idiopathic pulmonary fibrosis and in a repetitive bleomycin lung injury murine model of persistent fibrosis. Here, CD8A is linked to idiopathic pulmonary fibrosis.