Chronic T cell proliferation in brains after stroke could interfere with the efficacy of immunotherapies

Stroke is one of the leading causes of death and permanent disability worldwide (World Health Organization, 2017). Despite the enormous medical need, specific therapies for stroke patients are still limited to vascular recanalization approaches within the acute phase after stroke (Emberson et al., 2014; Fiehler and Gerloff, 2015; Hacke et al., 2008). In the search for alternative therapeutic strategies, post-stroke neuroinflammation has come into focus in current translational stroke research (Iadecola and Anrather, 2011). Neuroinflammation after stroke is a crucial pathomechanism contributing to secondary brain injury, neurodegeneration, and recovery (Iadecola and Anrather, 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.

Automated summary

Stroke is a major cause of death and permanent disability globally, with current therapies limited to vascular recanalization in the acute phase. Neuroinflammation has emerged as a key focus in translational research, playing a crucial role in post-stroke recovery and neurodegeneration.