Immune Tolerance for Autoimmune Disease and Cell Transplantation

Abstract

The undesired destruction of healthy cells, either endogenous or transplanted, by the immune system results in the loss of tissue function or limits strategies to restore tissue function. Current therapies typically involve non-specific immunosuppression that may prevent the appropriate response to an antigen, thereby decreasing humoral immunity and increasing the risks of patient susceptibility to opportunistic infections, viral reactivation, and neoplasia. The induction of antigen-specific immunological tolerance to block undesired immune responses to self- or allogeneic antigens, while maintaining the integrity of the remaining immune system, has the potential to transform the current treatment of autoimmune disease and serve as a key enabling technology for therapies based on cell transplantation.

Engineered erythrocytes covalently linked to antigenic peptides can protect against autoimmune disease

“…Because sustained immunosuppression increases the risk of infection, an important goal remains the development of antigen-specific immune intervention to achieve tolerance, while sparing desirable effector immune responses, such as those directed against pathogens (1). Administration of soluble, disaggregated proteins or peptides, apoptotic cells, or micro/nanoparticles chemically conjugated with antigenic peptide, as well as antibody fusion constructs, have been used with varying degrees of success (2)(3)(4)(5)(6)(7)(8). A challenge in the development of antigen-specific immune intervention is the delivery of the antigenic payload to the correct destination for processing, to establish long-lasting peripheral tolerance.…”

Tolerogenic Nanoparticles to Treat Islet Autoimmunity

“…It has been noted that general immunosuppression does not cure underlying autoimmunity [43–45]. Therefore, antigen-specific tolerance that does not affect the rest of the immune system and would avoid side effects is a preferable alternative [46]. …”

“…Transplant of either stem cell or deceased donor origin islet cells is a promising technique for curing T1D, especially for those suffering from severe hypoglycemia. Sadly, however, recipients of allogeneic islet grafts require lifelong immunosuppression to avoid host rejection of the transplanted cells [3, 46]. Our group and collaborators have explored the use of negatively charged antigen-coupled or encapsulating nanoparticles to induce tolerance in transplant models [122] and have used ECDI-treated donor splenocytes to tolerize recipients of islet transplants [124•].…”

Preparation of Complexes between Ovalbumin Nanoparticles and Retinoic Acid for Efficient Induction of Tolerogenic Dendritic Cells

“…Thus, antigen-specific immunotolerance therapy that induces specific tolerance toward allergens and auto-antigens has been gathering attention. [4][5][6] Tolerogenic dendritic cells (tDCs) play crucial role in the immunotolerance therapy. tDCs show semimatured phenotype, i.e., presenting antigen peptides via major histocompatibility complex (MHC) class II while keeping low level of expression of costimulatory receptors CD80/86.…”