Letter by Gauberti and Vivien Regarding Article, “Amplification of Regulatory T Cells Using a CD28 Superagonist Reduces Brain Damage After Ischemic Stroke in Mice”

The recent article by Na et al1 shows that amplification of regulatory T-cell (Treg) improves stroke outcome in both permanent and transient mechanical vascular occlusion (TMVO) models in mice. Surprisingly, Schuhmann et al2 published the exact opposite finding 1 month before, ie, amplification of Treg worsens stroke outcome by increasing thromboinflammation. One year after publication of a controversy in Stroke on the role of Treg in acute ischemic stroke, we thought how to explain this persisting discrepancy in preclinical research results? We thought that the basis for all the paradoxical results on Treg has not been correctly identified and can be resumed as follows: thromboinflammation is not a universal response to cerebral ischemia-reperfusion, but, rather, a specific feature of TMVO models.Treg are double-edged sword in acute ischemic stroke. On the one hand, they protect neurons from inflammation-related death and, on the other, they promote secondary microthrombosis (the final step of the thromboinflammatory reaction). Therefore, in permanent models (eg, without secondary microthrombosis), Treg are protective, as consistently shown by several studies. In …