Antigen-Specific Regulatory T Cell Therapy in Autoimmune Diseases and Transplantation.

Claudia Selck,Margarita Dominguez-Villar

doi:10.3389/fimmu.2021.661875

Abstract

Regulatory T (Treg) cells are a heterogenous population of immunosuppressive T cells whose therapeutic potential for the treatment of autoimmune diseases and graft rejection is currently being explored. While clinical trial results thus far support the safety and efficacy of adoptive therapies using polyclonal Treg cells, some studies suggest that antigen-specific Treg cells are more potent in regulating and improving immune tolerance in a disease-specific manner. Hence, several approaches to generate and/or expand antigen-specific Treg cells in vitro or in vivo are currently under investigation. However, antigen-specific Treg cell therapies face additional challenges that require further consideration, including the identification of disease-relevant antigens as well as the in vivo stability and migratory behavior of Treg cells following transfer. In this review, we discuss these approaches and the potential limitations and describe prospective strategies to enhance the efficacy of antigen-specific Treg cell treatments in autoimmunity and transplantation.

Highlights

Treg cells play an essential role in the maintenance of immune homeostasis by inhibiting pathological responses towards self-antigens and controlling potentially harmful inflammatory reactions following infections
chimeric antigen receptors (CARs)-engineered human CD4+ CD25+ Treg Reduced graft injury in a human skin xenograft model compared to polyclonal Treg transplantation mice cells specific for HLA-A2 cells
Different reports from animal models of type 1 diabetes (T1D) and rheumatoid arthritis (RA) demonstrate that T cell receptor (TCR) engineering can be successfully combined with the transduction of forkhead box P3 (FOXP3) in order to convert Teff lymphocytes into immunosuppressive antigen-specific Treglike cells [68, 82]. These preclinical studies are encouraging, the translation of TCR-engineered Tregs into the clinic is somewhat limited by their major histocompatibility complex (MHC) restriction and the need to isolate and identify antigen-specific and disease-relevant TCRs

Summary

Introduction

Treg cells play an essential role in the maintenance of immune homeostasis by inhibiting pathological responses towards self-antigens and controlling potentially harmful inflammatory reactions following infections. These treatments currently involve either the adoptive transfer of in vitro expanded Treg cells, or the administration of immunomodulatory interventions that promote the expansion and/or function of Treg cells in vivo (Figure 1).

Results

Conclusion