The Next Frontier of Regulatory T Cells: Promising Immunotherapy for Autoimmune Diseases and Organ Transplantations.

Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE

Original Publication: [Lausanne : Frontiers Research Foundation]

Autoimmune Diseases/*therapy ; Graft Rejection/*prevention & control ; Immunosuppression Therapy/*methods ; Immunotherapy, Adoptive/*methods ; Liver Transplantation/*methods ; Receptors, Chimeric Antigen/*immunology ; T-Lymphocytes, Regulatory/*immunology; Animals ; Extracellular Vesicles/immunology ; Graft Rejection/immunology ; Humans ; Immune Tolerance ; Interleukin-2/therapeutic use

Regulatory T cells (Tregs) are crucial in maintaining tolerance. Hence, Treg immunotherapy is an attractive therapeutic option in autoimmune diseases and organ transplantations. Currently, autoimmune diseases do not have a curative treatment and transplant recipients require life-long immunosuppression to prevent graft rejection. There has been significant progress in understanding polyclonal and antigen-specific Treg biology over the last decade. Clinical trials with good manufacturing practice (GMP) Treg cells have demonstrated safety and early efficacy of Treg therapy. GMP Treg cells can also be tracked following infusion. In order to improve efficacy of Tregs immunotherapy, it is necessary that Tregs migrate, survive and function at the specific target tissue. Application of antigen specific Tregs and maintaining cells' suppressive function and survival with low dose interleukin-2 (IL-2) will enhance the efficacy and longevity of infused GMP-grade Tregs. Notably, stability of Tregs in the local tissue can be manipulated by understanding the microenvironment. With the recent advances in GMP-grade Tregs isolation and antigen-specific chimeric antigen receptor (CAR)-Tregs development will allow functionally superior cells to migrate to the target organ. Thus, Tregs immunotherapy may be a promising option for patients with autoimmune diseases and organ transplantations in near future.
(Copyright © 2020 Terry and Oo.)

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United Kingdom MRC_ Medical Research Council

Keywords: antigen specific; autoimmune liver diseases; liver transplant; polyclonal; recruitment; regulatory T cell; tolerance

0 (Interleukin-2)
0 (Receptors, Chimeric Antigen)

Date Created: 20201019 Date Completed: 20210503 Latest Revision: 20211204

20221213

PMC7538686

10.3389/fimmu.2020.565518

33072105