Regulatory T Cell in Stroke: A New Paradigm for Immune Regulation

Abstract

Stroke is a common, debilitating trauma that has an incompletely elucidated pathophysiology and lacks an effective therapy. FoxP3+CD25+CD4+ regulatory T cells (Tregs) suppress a variety of normal physiological and pathological immune responses via several pathways, such as inhibitory cytokine secretion, direct cytolysis induction, and antigen-presenting cell functional modulation. FoxP3+CD25+CD4+ Tregs are involved in a variety of central nervous system diseases and injuries, including axonal injury, neurodegenerative diseases, and stroke. Specifically, FoxP3+CD25+CD4+ Tregs exert neuroprotective effects in acute experimental stroke models. These beneficial effects, however, are difficult to elucidate. In this review, we summarized evidence of FoxP3+CD25+CD4+ Tregs as potentially important immunomodulators in stroke pathogenesis and highlight further investigations for possible immunotherapeutic strategies by modulating the quantity and/or functional effects of FoxP3+CD25+CD4+ Tregs in stroke patients.

Some cross-talks between immune cells and epilepsy should not be forgotten

“…To investigate the role of T cells in TLE, Zhiguo et al used gene deficit mice to establish epileptic model; as a result: CD4/CD8 (-/-) mice showed the mildest seizure, CD8 (-/-) , wild-type mice displayed intermediate response, and CD4 (-/-) mice presented much more severe clinical features and 100 % early mortality. Histopathological detection in this study revealed the fewest pathological changes in CD4/CD8 (-/-) mice 7 days after KA-infusion [43]. Besides, Deprez's [55] and Zattoni's [7] studies also showed advanced spontaneous recurrent seizures (SRS) onset and delayed hippocampal destruction by neutrophils in RAG1-KO mice, indicating a neuroprotective role of T cells infiltrated in the epileptic focus.…”

“…Regulatory T cell (Treg) is an innate immunomodulator involved in various CNDs, including stroke, axonal injury, and neurodegenerative disease [43]. In vitro and in vivo studies have indicated that Tregs can suppress the production of peripheral neutrophil-derived matrix metalloprotease (MMP-9), which alleviates proteolytic damage of BBB [44].…”

Circulating brain derived neurotrophic factor (BDNF) and frequency of BDNF positive T cells in peripheral blood in human ischemic stroke: Effect on outcome

“…When these subgroups are compared with the control group there was no significant difference. Chen et al, 2013). But results from experimental animal models of stroke suggest that Tregs can traffic to the site of the stroke.…”

“…Adoptive transfer of Treg cells led to reduction of volume of ischaemia in experimental stroke (Brea et al, 2014). However, the role of Treg cells in recovery from stroke may be different at different time points after stroke (Chen et al, 2013;Kleinschnitz et al, 2013;Xu et al, 2013).…”

Immunopathogenetic Aspects of Ischemic Stroke

“…Обладая супрессорной активностью, Тreg через модуля-цию воспалительного процесса могут защищать ткани мозга от ишемического повреждения. Так, Тreg секретируют противовоспалительные цито-кины (TGF-β, IL-10), подавляющие системное и локальное воспаление; ингибируют выработку металлопротеиназы-9, предотвращая нарушения гематоэнцефалического барьера; ингибируют ак-тивность Т-клеток в мозговой ткани и на пери-ферии; подавляют активацию микроглии [18,68]. Усиление активности Тreg с помощью ингибито-ра гистоновой диацетилазы приводит к сокраще-нию размеров поражения мозговой ткани [69].…”