. 2025 Jun 12;13:e19450. doi: 10.7717/peerj.19450

Table 1. Preclinical and clinical studies demonstrating increased efficacy of adoptive Tregs therapies in neurological autoimmune diseases.

Pre-clinial studies
Disease	Model	Treg population	Evidence of functional manifestation	Ref.
MS	C57BL/6 mice	CD4⁺CD25⁺CD62L^high T cells from peripheral LN of mice	Significant protection from the clinical development of MOG₃₅₋₅₅induced EAE compared to non-Treg (CD25-)	Kohm et al. (2002)
MS	SJL/J, C57BL/6J and IL-10-deficient mice on a C57BL/6J background	CD4⁺CD25⁺ T cells from spleen and LN of mice	CD4⁺CD25⁺ Tregs suppress the immune responses of pathogenic T cells of PLP peptide-immunized EAE mice through secreting IL-10	Zhang et al. (2004)
MS	C57BL/6 (Ly5.2⁺ and Ly5.1⁺) mice	CD4⁺CD25⁺ T cells from the peripheral LN of mice by co-culturing with irradiated splenic APC and anti-CD3	CNS-derived CD4⁺CD25⁺ T cells suppress induction of EAE	McGeachy, Stephens & Anderton (2005)
MS	HLA-DR15 transgenic mice	Engineered TCR MBP-specific Tregs in vitro from MS patients	Amelioration of EAE symtoms in MOG-immunized DR15 transgenic mice and suppression of autoimmune pathology in EAE	Kim et al. (2018)
MS	C57BL/6 mice	GFP/CARαMOG-Foxp3-engineered CD4⁺ T cells in vitro from the mice	Prominent inhibiton capacity in vitro and myelin recovery in mice treated with engineered Tregs compared to controls	Fransson et al. (2012)
MS	B10.PL, B10.PL×SJL, transgenic mice	CD4⁺CD25⁺ T cells in vitro culture with anti-CD3/CD28 beads from TCR-transgenic mice	Tregs prevent disease relapse when given after the onset of clinical EAE (no effect with polyclonal Tregs)	Stephens, Malpass & Anderton (2009)
MS	HLA-DR15 transgenic mice on a C57Bl/6 background	Human Tregs expressing functional single-chain chimeric antigen receptors (scFv CAR), targeting either MBP or MOG	Potent suppression ability of autoimmune pathology in EAE compared to OB2F3-TCR Tregs	DePaula Pohl et al. (2020)
MG	Lewis rats 6–7 weeks of age	Ex vivo generated CD4⁺ Tregs with anti-CD3/ CD28 beads and IL-2 from spleens of naive rats	Inhibition the progression of EAMG and down-regulation of humoral AChR-specific responses	Aricha et al. (2008)
MG	Rats	CD4⁺CD25⁺ Tregs in vitro culture with anti-CD3/ CD28 beads, TGF-β and IL-2 from healthy rats	Significant inhibitory effect on EAMG	Souroujon et al. (2012)
MG	Lewis rats aged 8–10 weeks	CD4⁺CD25⁺ Tregs sorted by co-culturing with DCs from spleens of rats	Significant suppressive effect of EAMG by autologous Tregs	Aricha et al. (2016)
GBS	Lewis rats	CD4⁺CD25⁺ Tregs with anti-CD3/CD28 beads, IL-2, TGF-β and rapamycin	Reducction of inflammatory cells infiltration in the sciatic nerve, as well as myelin and axonal damage of EAN	Wang, Cui & Qian (2018)
GBS	Lewis rats	Alloantigen specific CD4⁺CD25⁺ Tregs by ex vivo activation of PNM and rIL-2	Strong inhibition effect on EAN	Tran et al. (2020)
NMOSD	C57BL/6 mice	CD4⁺CD25⁺ Tregs from spleens of mice	Suppression of inflammatory response and promotion of neuroprotection and regeneration	Ma et al. (2021)
Clinical studies
Disease	Methods	Phases	NCT number and status	Ref.
MS	autologous polyclonal expanded Treg	Phase 1	EudraCT: 2014-004320-22; Recruiting	Chwojnicki et al. (2021)

Notes.

Abbreviations

Treg: regulatory T cell
MS: multiple sclerosis
MG: myasthenia gravis
GBS: Guillain-Barré syndrome
NMOSD: neuromyelitis optica spectrum disorders
LN: lymph nodes
MOG: myelin oligodendrocyte glycoprotein
EAE: experimental autoimmune encephalomyelitis
IL: interleukin
PLP: proteolipid protein
APC: antigen-presenting cell
CNS: central nervous system
HLA: human leukoyte antigen
TCR: T cell receptor
MBP: myelin basic protein
GFP: green fluorescent protein
CAR: chimeric antigen receptor
Foxp3: forkhead box protein 3
EAMG: experimental autoimmune myasthenia gravis
AChR: acetylcholine receptor
TGF-β: transforming growth factor-β
DCs: dendritic cells
PNM: peripheral nerve myelin
EAN: experimental autoimmune neuritis
NCT: national clinical trial