Regulatory T Cells are Cerebroprotective in Acute Experimental Stroke


A recent Nature Medicine study by Arthur Liesz et al. indicates that regulatory T cells (Treg) are cerebroprotective after experimental brain ischemia or stroke, and that interleukin (IL)-10 appears to be the major mediator of the cerebroprotective effects.

Recent evidence indicates that inflammatory mechanisms such as up-regulation of pro-inflammatory cytokines and leukocytes’ invasion in the brain contribute to the ischemic brain damage. It is also known that the neuroendocrine-immune interactions contribute to a serious immune dysfunction after stroke, which includes severe systemic immunodepression related to life-threatening infections.

Thymus-derived CD4+CD25+Foxp3+ Treg cells play a key part in controlling immune responses by altering the activity of antigen-presenting cells via direct interaction and through secretion of anti-inflammatory cytokines, including IL-10 and transforming growth factor (TGF)-β.

The overall immune changes and the mechanisms of the immune dysfunction after brain ischemia or stroke remain poorly understood. This also includes the question of whether and how Treg are involved in cerebral ischemia.

In the Nature Medicine study, Arthur Liesz and colleagues from the Department of Neurology, University of Heidelberg, Heidelberg, Germany investigated the role Treg cells play after ischemic experimental stroke. The authors report that Treg prevent secondary infarct growth by counteracting excessive production of proinflammatory cytokines and by modulating invasion and/or activation of lymphocytes and microglia in the ischemic brain.

The German research group has found that Treg cells antagonize enhanced TNF-α and IFN-γ production, which induce delayed inflammatory brain damage, and that Treg cell–derived secretion of IL-10 is the key mediator of the cerebroprotective effect via suppression of proinflammatory cytokine production.

The study is perhaps the first to examine the role of Treg cells in acute cerebral ischemia, and reveals a previously unrecognized role of Treg cells in mediating cerebral protection after stroke. Thus, it may provide new insights into the endogenous adaptive immune response after acute brain ischemia.

Source: Nat Med 2009, 15:192
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