Table 1.

Strategies for induction of immune tolerance in neuromyelitis optica.

Method	Mechanism of action
Inverse DNA vaccination	Vaccination with autoantigen-encoding DNA to attenuate activity of autoreactive B and CD8+ T cells.
Anti-autoreactive T cell vaccination	Vaccination with receptor idiotype-restricted CD41/ CD251/FoxP3 Tregs, IL-10-secreting CD41 Tr1cells, and CD81 cytotoxic T cells to modulate and reduce the activity of autoreactive T cell clones.
Dendritic cell vaccination	Administration of immature dendritic cells engineered to maintain a tolerogenic phenotype to inhibit Th1 and Th17 cells and to induce Tregs production of IL-10.
Antigen-coupled apoptotic leukocytes or liposomes	Administration of antigen-apoptotic cell (APC or PMN) or liposome complexes to induce tolerogenic antigen presentation, T cell anergy and upregulation of Tregs.
T cell receptor engineering	Engineering of T cell receptor (TCR) to express a single chain variable fragment from a known antibody to prevent off-target major histocompatibility complex (MHC) restriction.
Regulatory T cell induction	Administration of autologous polyclonal CD4+CD25+Foxp3+ regulatory T cells to modulate immune responses to autoantigens.
Regulatory B cell induction	Adoptive transfer of TGF-β-producing B cells (Bregs) to attenuate disease related autoimmunity by targeting pathogenic cells and secretion of IL-10.
Oral/mucosal tolerization	Oral administration of autoantigen to stimulate gut-associated T regulatory cells.
Adoptive transfer	Adaptive transfer of AQP4-specific T and B cells to recipients for the purpose to modulate pathogenic effector cells via IL-10 and TGF-β.
Anti-idiotypic networks	Targeting of antigen-binding Fab domains of anti-AQP4 antibody by recombinant anti-idiotypic antibodies.
Passive tolerization	Therapeutic use of aquaporumab, a recombinant monoclonal antibody that functions as a competitive inhibitor to anti-AQP4 antibodies because of its high affinity for AQP4 and lack of cytotoxic properties.
Hematopoietic stem cell transplantation	Immune ablative therapy with hematopoietic stem cell rescue aiming to destroy the autoimmune clones and to induce immune reset and long- term immune tolerance.
TIMP	Intravenous administration of tolerogenic immune-modifying PLG nanoparticles encapsulating autoantigen to induce specific T cell anergy and upregulation of iTregs and Tr1 cells.