Chronic T cell proliferation in brains after stroke could interfere with the efficacy of immunotherapies.
Steffanie HeindlAlessio RicciOlga CarofiglioQihui ZhouThomas ArzbergerNikolett LenartNicolai FranzmeierHortobágyi TiborPeter T NelsonAnn M StoweAdam DenesDieter EdbauerArthur LieszPublished in: The Journal of experimental medicine (2021)
Neuroinflammation is an emerging focus of translational stroke research. Preclinical studies have demonstrated a critical role for brain-invading lymphocytes in post-stroke pathophysiology. Reducing cerebral lymphocyte invasion by anti-CD49d antibodies consistently improves outcome in the acute phase after experimental stroke models. However, clinical trials testing this approach failed to show efficacy in stroke patients for the chronic outcome 3 mo after stroke. Here, we identify a potential mechanistic reason for this phenomenon by detecting chronic T cell accumulation-evading the systemic therapy-in the post-ischemic brain. We observed a persistent accumulation of T cells in mice and human autopsy samples for more than 1 mo after stroke. Cerebral T cell accumulation in the post-ischemic brain was driven by increased local T cell proliferation rather than by T cell invasion. This observation urges re-evaluation of current immunotherapeutic approaches, which target circulating lymphocytes for promoting recovery after stroke.
Keyphrases
- cerebral ischemia
- subarachnoid hemorrhage
- cell proliferation
- brain injury
- blood brain barrier
- clinical trial
- resting state
- white matter
- peripheral blood
- atrial fibrillation
- cell cycle
- endothelial cells
- functional connectivity
- drug induced
- pi k akt
- type diabetes
- adipose tissue
- lipopolysaccharide induced
- oxidative stress
- multiple sclerosis
- stem cells
- ischemia reperfusion injury
- insulin resistance
- mesenchymal stem cells
- lps induced
- signaling pathway
- induced pluripotent stem cells
- nk cells
- smoking cessation