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Table 3 Stroke therapy related to T cells

From: The immune response of T cells and therapeutic targets related to regulating the levels of T helper cells after ischaemic stroke

Target therapy Experimental model Function Molecular mechanism Reference
Cytokines, small molecules, neutralizing antibodies, cell epitopes
 IL-4/rIL-4 injected subcutaneously Mouse model Increasing Th2 cells and promoting polarization of microglia to the healing M2 phenotype Exerting the function of IL-4 Zhao et al. [124]
 IL-15/IL-15 neutralizing antibody injected subcutaneously Mouse model Decreasing NK, CD8+ T and CD4+ T cells infiltrating the brain Exerting the function of IL-15 Lee et al. [126]
 IL-21/IL-21 receptor Fc protein injected intraperitoneally Mouse model Blocking T cell-derived IL-21 to reduce CD4+ and CD8+ cells infiltrating the brain and attenuate neuronal autography Exerting the function of IL-21 Clarkson et al. [127]
 IL-33/IL-33 injected intraperitoneally Male mouse model Suppressing Th1 cell response as well as improving Treg cell response Downregulating the expression of the transcription factor T-bet and upregulating the expression of GATA-3 and Foxp3 Xiao et al. [128]
 PD-1/humanized anti-PD-L1 antibody Mouse model/clinical trial Increasing the appearance of CD8+ regulatory T cells in the lesioned brain and decreasing CNS infiltrating immune cells Unclear Bodhankar et al. [129], Zhang et al.
 DHA/DHA injected intraperitoneally Mouse model Attenuating the infiltration of T cells into injured brain tissue and promoting polarization of microglia to the healing M2 phenotype Reducing the production of CCL3, CCL17, CXCL10 and CXCL12 to decrease the quantity of T cells Cai et al. [130]
 GSF/GSF injected intraperitoneally Rat model Attenuating the recruitment of T cell in post-stroke injured brain Reducing blood-brain barrier disruption Dietel et al. [131]
 CXCL14/2-methoxyestradiol injected intraperitoneally Rat model Inducing Treg differentiation Promoting accumulation of iDC to secrete IL-2 to induce Treg differentiation Lee et al. [132]
 ACC1/(caloric restriction) Mouse model Balancing peripheral regulatory T cells/T helper 17 (Th17) cells Inhibiting the ACC1 enzyme Wang et al. [133]
 CD28/CD28SA injected intraperitoneally Mouse model Expanding and amplifying Treg cells that produce IL-10 Boosting the production of IL-10 Na et al. [134]
 TLR/The antibodies of TLR2, TLR4 and TLR8 Vitro study Reducing the activation of T cells Unclear Tang et al. [135]
 RTLs/RTL551, RTL100 ] injected subcutaneously Male DR2-Tg mice Inhibiting the activation or infiltration of CD3+ T cells and other proinflammatory cells Modulating T cell functional properties and blocking immune cells infiltrating the brain Zhu et al. [136]
 Glycyrrhizin (Gly)/injected intraperitoneally Mouse/rat model Inhibiting the activation of CD8+ T and CD4+ T cells Inhibiting HMGB1 release, which promoted T cell proliferation Xiong et al. [137]
 Exogenous vitamin D3/injected intraperitoneal injection Mouse model Reducing Th17/γδ T cell response and increasing Treg cell response Reducing the expression of proinflammatory mediators IL-6, IL-1β, IL-23a, TGF-β and NADPH oxidase-2 and expression of the transcription factor, ROR-γ Evans et al. [138]
 Intravenous cellular/injected intravenously (MAPCs) Animal model/clinical trial Reducing proinflammatory cells including CD3+ T, CD4+ T and CD8+ T cells and promoting Tregs Relating to multiple mechanisms of action Mays et al. [139]
 Treg/antibiotic-induced intestinal flora alteration Mouse model Increasing regulatory T cells and reducing IL-17+ γδ T cells Altering dendritic cell activity to induce Treg cell differentiation more effectively Benakis et al. [140]
 Treg/adoptively transferred Treg Mouse model Increasing the number and/or function of Treg Unclear Xia et al. [141]
 Brain antigen/intranasal instillation MBP Male rat model Suppressing Th1 response and increasing the probability of Tr1, Th3 or other Tregs responses Inducing mucosal tolerance Gee et al. [142]
E-selection SHR-SP rat model Chen et al. [143]
MOG Female rat model Frenkel et al. [144]
 Levodopa/benserazide/injected intraperitoneally Rat model Reducing CD8+ cells infiltrating the injured brain Reducing the expression of ICAM-1 on endothelial cells in the brain to inhibit adhesion of cytotoxic T cells infiltrating the brain parenchyma Kuric et al. [145]
 Natalizumab/injected intravenously Clinical trial Blocking T cell infiltration into the brain Blockade of the α4-β1 integrin on leukocytes Veltkamp et al. [146], Fu et al. [147]
 Fingolimod/orally Clinical trial Reducing peripheral lymphocytes An oral S1P receptor modulator that sequesters lymphocytes to lymph nodes Veltkamp et al. [131], Fu et al. [147]