Table 3 Myasthenia gravis treatment approaches using Treg augmentation based on pre-clinical models
From: Regulatory T cells in multiple sclerosis and myasthenia gravis
Therapeutic modality | Intended Treg augmentation | Approach | Outcome | Reference |
|---|---|---|---|---|
GM-CSF | Expand functional Tregs via Tolerogenic DCs | 77-year-old male with myasthenia crisis untreated with conventional treatments. GM-CSF 750 μg daily for 2 days, then 250 μg daily for 3 days, then 5 more 250 μg doses daily in week 7–8 | Cessation of myasthenic crisis ↑ strength weaned from ventilator | [198] |
EAMG (tAChR) in C57BL/6. GM-CSF daily on days 0–9 and 37–41 | ↓ clinical score ↓ weight loss ↓ anti-AChR Ab ↑ IL-10, -4, FoxP3 ↓ IFN-g | [200] | ||
IL-2/mAb complexes | Activate peripheral Treg, activate and TFR in GC to suppress TFH and B cells, increase Treg migration to GC | EAMG (tAChR) in thymectomized C57BL/6. IL-2 complexes twice weekly | ↓ clinical score ↓ autoantibodies ↓ CD19 cells ↑ TGF beta ↓ IFN-g | [189] |
Emperically supported treatments yet to be used in EAMG pre-clinical models | ||||
OX40L Jagged-1 Co-treatment | Selectively expand functional Tregs in TCR-independent manner, modulate CD46 Treg stimulation | EAMG (tAChR) C57BL/6. Adoptive transfer of Tregs from GM-CSF treated EAMG mice into EAMG mice | ↓ clinical score ↓ auto antibodies ↑ AChR content | [67] |
Experimental autoimmune thyroiditis (via murine thyroglobulin) CBA/j. Adoptive transfer of OX40L + Jagged1+ from GM-CSF treated bone marrow DCs (control: non treated and single OX40L positive) | ↓ pathology in double positive only ↑ Treg in double positive only | [157] | ||
TGF-beta | Induce iTregs | Lupus-prone mice (NZB/NZW F1). Adoptive transfer of CD4 + CD62L + CD25-CD44low cells stimulated with anti-CD3 and anti-CD28 in presence of IL-2 and TGF-beta | ↓ multiple auto antibodies | [208] |
Ex vivo human MG peripheral blood mononuclear cells. Stimulated with TGF-beta | ↓ mRNA for IFN-gamma, IL-4, -6, TNF alpha, TNF beta Suppressed AChR-reactive IFN-gamma and IL-4 secreting cells | [209] | ||