TABLE 1.

Contribution of the adaptive immune system in primary neurodegenerative diseases.

Primary neurodegenerative diseases	Neurodegeneration	Regeneration
Alzheimer’s disease	Rag-5xfAD mice show enhanced Aβ pathology and neuroinflammation (Marsh et al., 2016).	AB-specific Th2 cells promote neurological recovery (Cao et al., 2009).
	IFN-y producing Th1 cells enhance microglial activation and Aβ deposition (McQuillan et al., 2010; Browne et al., 2013).	IL-17 depletion enhances neural precursor cell expression and synaptic transmission (Liu et al., 2014).
	Depletion of Tregs in mice accelerates AD-related cognitive dysfunction (Baek et al., 2016; Dansokho et al., 2016).	Adoptive transfer of Tregs reduces Aβ deposition and reverses cognitive deficits (Baek et al., 2016).
Parkinson’s disease	SCID, Rag1 KO, TCR B KO, CD4 KO but not CD8 KO mice show attenuated dopaminergic cell death (Benner et al., 2008; Brochard et al., 2009; Gonzalez et al., 2013).	Copolymer 1 immunized T cells administered to MPTP mice limited neuronal loss (Schori et al., 2001; Benner et al., 2004).
	Adoptive transfer of T cells from mice immunized with α-synuclein exacerbate MTPT (Reynolds et al., 2010).	Adoptive transfer of activated Tregs to MPTP provides 90% neuronal protection (Reynolds et al., 2007).
	IL-17 increases cell death in iPSC-derived neurons from PD patients (Sommer et al., 2019).	GM-CSF administration increases Tregs, limits inflammation and increases neuroprotection (Kosloski et al., 2013; Gendelman et al., 2017; Schutt et al., 2018).
	Suppression of CD4 T cell infiltration ameliorates PD symptoms (Qin et al., 2016).
Amyotrophic lateral sclerosis	A Th1/Th17 immune response correlates with disease progression and severity (Saresella et al., 2013; Jin et al., 2020).	Reconstitution with CD4+ T cells in SOD1G93A mice increases neuroprotection (Beers et al., 2008).
	In the SOD1G93A model, CD8+ T cell ablation leads to a reduction in motor neuron loss (Coque et al., 2019).	Disease progression reduces Tregs (Beers et al., 2011).
	A2BG2 glycan is increased in IgG antibodies for SOD1G93A mice, increasing neuronal cytotoxicity and death (Edri-Brami et al., 2015).	Adoptive transfer of activated Tregs to SOD1G93A mice delays motor function loss and enhances survival (Banerjee et al., 2008).