Table 1 Peripheral Treg expansion for disease combating neuroprotection in different neurodegenerative animal models
From: Harnessing regulatory T cell neuroprotective activities for treatment of neurodegenerative disorders
Treg expansion | Disease | Experimental model | Effects |
|---|---|---|---|
Adoptive transfer | MS | EAE | Resistance to reinduction of EAE [196]. Mice are disease-free [197]. |
AD | 3xTg | Reduced Aβ plaque deposition and improved behavior [23] | |
PD | MPTP | Attenuated Th17 neurodestructive and microglial inflammatory responses and induced nigrostriatal protection [1] | |
ALS | mSOD1/RAG2−/−, mSOD1G93 | Tregs isolated from disease mice prolonged survival [21, 198, 199] | |
Stroke | MCAO | Reduced brain infarction [200], attenuated inflammation and BBB damage [201]. Exerted early neuroprotection without entering the brain [202]. Promotion of neurogenesis [203] and remyelination [18]. | |
Low dose IL-2 | MS | EAE | Pre-treatment only attenuated EAE [204]. |
AD | APP/PS1, APP/PS1ΔE9 | Restored cognitive function, increased number of plaque associated microglia [175] and astrocytes [177] | |
GM-CSF | AD | APP/PS1 | Increased Aβ clearance and improved cognition. Recruitment of microglia surrounding Aβ plaque, improved synaptic plasticity and neurogenesis [17] |
PD | MPTP | Protected tyrosine hydroxylase immunoreactive (TH+) neurons in SN, attenuated microglial activation and improved motor functions [26, 192] | |
Vasoactive intestinal peptide (VIP) | MS | EAE | Inhibited encephalitogenic T cell activation and slowed disease [144] |
PD | MPTP | Attenuated microglial activation and spared TH+neurons in SN. Phenotypic shift of effector cells to Treg was observed [25] | |
Fingolimod | MS | EAE | Inhibited peripheral Teffs entry inside the CNS by sequestering them into lymph nodes but allowed Tregs entry [145, 146] |
AD | 5xFAD | Decreased amyloid plaque and microglia activation and promoted anti-inflammatory neuroprotective responses [179] | |
IL-2/IL-2 antibody complex (IL-2/IL-2Ab) | MS | EAE | Development of resistance to induction of EAE [205] and reduced disease severity [206] |
ALS | mSOD1G93A | Slowed down disease progression rate and increased survival period [207] | |
Stroke | MCAO | Early Treg protective effects independent to their brain penetration by suppressing peripheral Teffs. Also attenuated central neuroinflammation and protected against brain injury [208]. | |
Traumatic brain injury (TBI) | controlled cortical impact (CCI) | Attenuated neutrophil infiltration and inflammation leads to improved neurological recovery [209]. | |
Bee venom phospholipase A2 | AD | 3xTg | Decreased Aβ deposits in hippocampus and enhanced cognitive function. Microglia deactivation and reduced CD4+ T cell infiltration [178, 210] |
PD | MPTP | Induced microglia deactivation and attenuated CD4+ T cell infiltration [189, 195, 211] | |
Ginsenoside Rg1 | PD | MPTP | Inhibited microglia activation and CD3+ T cell infiltration [193] |
Intravenous immunoglobulin (IVIg) | MS | EAE | Prevented CNS infiltration of Teffs and almost completely protected mice from EAE [143] |
Atorvastatin | Stroke | MCAO | Prevented infarct and glia activation [212] |