Extended Data Fig. 5. uPAR CAR T cells are not associated with signs of tissue damage in aged tissues and do not exacerbate spontaneous age-related histological changes in lung, liver and kidneys.

Mice received cell infusions at 18–20 months and were sacrificed 20 days after infusion of the indicated T cells. Sections were stained with hematoxylin and eosin. Aged mice showed mononuclear leukocytic aggregates composed predominantly of lymphocytes and plasma cells in tissues in an age dependent manner. These leukocytic aggregates were more frequently observed in tissues from uPAR-m.28z CAR T- treated aged mice than tissues from control aged mice and were not associated with necrosis and/or degeneration in tissues from both experimental and control aged mice. These lymphocytic and plasmocytic aggregates in tissues are often observed in naïve aged mice and are considered spontaneous background findings in longitudinal aging studies in mice^50,51. a, Representative sections of normal cerebral cortex and meninges at the level of the posterior hypothalamus (inset: hippocampus). b. Histology of normal cardiomyocytes and interstitium in myocardium (inset: ventricles and interventricular septum). c. Representative histology of normal lungs showed dense aggregates of lymphocytes and fewer plasma cells and macrophages around bronchioles or vasculature (inset: pulmonary lobes). d. The liver from aged mice showed accumulation of lymphocytic and histiocytic aggregates in portal to periportal regions (Inset: hepatic lobe). e. Histology of the kidneys showed accumulation of lymphocytes and plasma cells in the renal interstitium (n & o) and around blood vessels (inset: renal cortex, medulla, and pelvis). f. Representative sections of normal pancreatic acini (exocrine pancreas) and islets of Langerhans (endocrine pancreas; inset: pancreatic lobule). Images were captured at 4x (insets) and 40x magnifications. Results of 1 independent experiment (with n = 3 per group).