Gu et al. (2012). This study explored the post-ischemic function of all subsets of T cells, aiming at clarifying the protective or detrimental roles of distinctive subsets after stroke. In this study, CD8+ cytotoxic T cells, CD4+ Th1 cells, CD4+ Th2 cells, and Tregs were evaluated both in vivo and in vitro, by means etc of genetic knockout of each subset and coculture of neurons with splenocytes from each knockout. As was illustrated in this experiment, elimination of Treg did not influence the outcome, yet deficiency of Th1 would attenuate while Th2 knockout would aggravate inflammatory response in vivo and neuronal death in vitro.Stubbe et al. (2013). This study was mainly focused on the accumulation, proliferation, and function of endogenous Tregs in a late phase after stroke.

By means of fluorescence activated cell sorting analysis and immunohistochemistry, the authors demonstrated that after MCAO, Tregs began to accumulate in the infarct and peri-infarct areas on day 7, and the ipsilesional accumulation persisted till day 30. Treg proliferation in the infarct areas increased throughout days 7 and 14 before its declination to a nearly normal level by day 30. Moreover, in order to clarify the late function of Tregs, 30min MCAO was performed followed by anti-CD25 mAb administered on days 3 and 14. Infarct volume was measured by MRI on days 3 and 27, and neural function was evaluated by gait analysis on days 14 and 27, but no significant difference was observed between the delayed Treg depletion group and controls.4. Discrepancies and DiscussionAs mentioned above, Tregs yield to profound inconstancy.

The controversial topic has triggered intensified debate and discussion recently. Outcome of current studies in murine model was summarized in Table 1. Table 1Outcome of current studies in murine model.4.1. Whether Endogenous Tregs Depletion Benefits or Exacerbates the OutcomeOne of the major discrepancies posed by Liesz et al. [55] and Kleinschnitz et al. [50] is whether endogenous Tregs are relevant to secondary infarct growth after stroke. Liesz et al. proved that Treg depletion was associated with secondary infarct growth by day 7, although these effects would not become evident within the first 3 days, which was consistent with the neutral report from Ren et al. [60] and Gu et al. [61], whereas in the experiment conducted by Kleinschnitz et al.

, Treg depletion led to a better outcome within 24 hours and Entinostat no progression occurred in both groups out to 1 week.A plausible explanation for the inconsistency may be attributed to the ischemic duration and measured time because specific cell types of the immune system might be differentially relevant in different models of stroke [52]. The most part of the study conducted by Liesz et al. was based on a permanent MCAO mouse model inducing cortical infarction around 15mm3 in size, while in the experiment reported by Kleinschnitz et al.