Revisiting regulatory T cells for stroke therapy

Abstract

Stroke is a leading cause of death and long-term disability. T cells have been extensively studied for their dual role in regulating immunity and inflammation following stroke. In this issue of the JCI, Cai, Shi, et al. demonstrated that CD8+ regulatory-like T cells (CD8+ TRLs) are one of the earliest lymphocyte subtypes to enter the brain after experimental ischemic stroke. Using a mouse model of stroke and comprehensive experimental approaches, the authors found that CD8+ TRLs reduced both brain damage and functional deficits in both young and aged mice. These unique early responding regulatory T cells may also play a role in a wide array of other T cell-mediated neurological disorders.

Figure 1. CD8⁺ TRLs confer early protection in the ischemic brain following stroke.

Cai, Shi, et al. (16) showed that brain CD8⁺ TRLs are remarkably increased in the early phase of stroke, contributing to the amelioration of brain damage and improving functional recovery in mice. CXCR3 was upregulated in circulating CD8⁺ TRLs and CXCR3-CXCL10 interactions were critical for the infiltration of the ischemic brain tissues by CD8⁺ TRLs. Days after stroke, CD8⁺ TRLs from the ischemic site showed increased LIF receptor, ETGF, and IL-10, which critically regulated the neuroprotective effect. Figure illustrated by Rachel Davidowitz.