Treg cell-based therapies: challenges and perspectives


Cellular therapies using regulatory T (Treg) cells are currently undergoing clinical trials for the treatment of autoimmune diseases, transplant rejection and graft-versus-host disease. In this Review, we discuss the biology of Treg cells and describe new efforts in Treg cell engineering to enhance specificity, stability, functional activity and delivery. Finally, we envision that the success of Treg cell therapy in autoimmunity and transplantation will encourage the clinical use of adoptive Treg cell therapy for non-immune diseases, such as neurological disorders and tissue repair.

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Fig. 1: Mechanisms of action of effector T cells versus Treg cells.
Fig. 2: Various Treg cell products for Treg cell-based therapy.
Fig. 3: Characteristics of recombinant T cell receptors versus chimeric antigen receptors.
Fig. 4: The future of Treg cell-based therapy.


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Correspondence to Jeffrey A. Bluestone.

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J.A.B. is a stock holder and member of the Board of Directors on Rheos Medicines; a stock holder and member of the Board of Directors for Provention Bio; and a stock holder and member of the Scientific Advisory Boards of Vir Therapeutics, Arcus Biotherapeutics, Quentis Therapeutics, Solid Biosciences and Celsius Therapeutics (Founder). J.A.B. owns stock in MacroGenics Inc., Vir Therapeutics, Arcus Biotherapeutics, Quentis Therapeutics, Solid Biosciences and Celsius Therapeutics. C.R. and L.T.V. declare no competing interests. J.A.B is the President and CEO of a newly formed biotech company targeting Treg therapy for the treatment of autoimmune and other immune disorders.

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Direct allospecificity

A process by which donor-derived antigen-presenting cells present allogeneic major histocompatibility complex–peptide complexes.

Indirect allospecificity

A process by which host-derived antigen-presenting cells present self-major histocompatibility complex–allogeneic peptide complexes.


A process whereby lymphocytes physically extract surface molecules from antigen-presenting cells.

Infectious tolerance

A phenomenon in which a tolerance-inducing state is transferred from one cell population to another.


The presentation of limited clonal variation.

Domain swap interface

The interface of a three-dimensional process by which two identical protein chains exchange part of their structure to form an intertwined dimer or higher-order oligomer.

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Raffin, C., Vo, L.T. & Bluestone, J.A. Treg cell-based therapies: challenges and perspectives. Nat Rev Immunol (2019).

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