CD4+FoxP3+ regulatory T-cells in cerebral ischemic stroke

Abstract

Experimental cerebral ischemic stroke is exacerbated by inflammatory T-cells and is accompanied by systemic increases in CD4+CD25+Foxp3+ regulatory T-cells (Treg). To determine their effect on ischemic brain injury, Treg were depleted in Foxp3(DTR) mice prior to stroke induction. In contrast to a recent Nature Medicine report, our results demonstrate unequivocally that Treg depletion did not affect stroke infarct volume, thus failing to implicate this regulatory pathway in limiting stroke damage.

Figure 1

Characterization of Foxp3⁺ Treg cell ablation in Foxp3^DTR mice. (A) On day 3 (after 2 DT or Vehicle treatments) and (B) on day 7 (after 3 DT or Vehicle treatments), mice were euthanized and lymphoid organs removed. Flow cytometric analysis of blood, LN-derived cells and splenocytes shows efficient depletion of Foxp3⁺ cells in DT-treated Foxp3^DTR mice compared with Vehicle-treated control mice (upper right quadrant). The percentage of cells in each quadrant is indicated. *Vehicle vs. DT treatment, p<0.001.

Figure 2

Depletion of Treg cells does not change ischemic lesion volume. (A) Scheme for experimental design. (B) Infarct volume at 96h reperfusion after 60min MCAO in male mice, (C) female mice and (D) combined data from both genders.