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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]