Infarct-associated oligoclonal T cell expansion in chronic experimental stroke across age, sex, and models.

Ischemic stroke induces prolonged T cell accumulation within injured brain tissue, yet it remains unclear whether these cells reflect nonspecific inflammatory persistence or organized adaptive immune responses. To define the clonal architecture of post-stroke T cells, we performed genomic DNA-based bulk T cell receptor (TCR) immunosequencing of CDR3α and CDR3β repertoires from infarcted brain and spleen during the chronic phase of experimental stroke across age and sex. TCRβ repertoires were further examined across three ischemic stroke models reproduced independently at sites in the United States and Europe. Chronic infarct tissue consistently exhibited oligoclonal T cell expansion across age, sex, stroke models, and laboratories; spleen and blood remained broadly polyclonal. Dominant clonotypes occupied a substantial fraction of the infarct repertoire, revealing a structured clonal architecture within the injured brain. Computational annotation identified recurrent sequence similarities to self-associated TCRs, including receptors linked to myelin, nuclear, and insulin-related antigens, although many expanded clonotypes lacked database matches. These annotations are presented as hypothesis-generating rather than evidence of antigen specificity. Together, these findings demonstrate that chronic ischemic brain injury is associated with a reproducible, infarct-associated clonal T cell signature whose conserved architecture is consistent with antigen-driven selection, although stochastic or cytokine-driven expansion cannot be excluded. The accompanying publicly available TCR repertoire dataset provides a clonotype-resolved reference resource for future investigations of antigen specificity and adaptive immune dynamics in chronic post-stroke neuroinflammation.