The Regulatory T-Cell Therapies (Tregs) are a mature subpopulation of T-cells that play a critical role in mediating immunological tolerance to self-antigens and suppress immune responses that are harmful to the host, thereby, enabling homeostasis. These mainly develop in thymus from CD4+ thymocytes and are mainly of three types: natural Tregs, adaptive Tregs and invitro Tregs. Tregscan either be directly administered or can be transduced with T cell receptor (TCR) or chimeric antigen receptor (CAR) which have high affinity to target antigens. In recent years, Treg based therapies have become a research hotspot in the field of immunotherapy due to their ability to prevent / delay graft rejection and control autoimmune responses generated post adoptive transfer in vivo.
Mechanism of Tregs
Tregs mediate the suppression of immune responses by several molecular mechanisms to regulate autoimmune responses and stimulate immune suppression.
Inhibition of Cytokine Production: Tregs have the ability to activate various immunoregulatory cytokines, including IL-10, TGFβ and interleukin-35 (IL-35).
Interaction with Dendritic cells: The interaction of Tregs with DCs leads to the production of INF-γ, a potent inducer of indoleamine 2,3-dioxygenase (IDO) which gradually leads to apoptosis of effector T cells
Metabolic Disruption: Treg-mediated metabolic disruption occurs by the following three mechanisms- Inhibition of the Proliferative Response by Competition for Interleukin 2 (IL-2), cAMP-Mediated Immunosuppression, Immunosuppression Mediated by the 2A Adenosine Receptor:
Cytolysis of Effector Cells: Tregs produce a glycoprotein, called perforin, and a serine protease, known as granzyme B which induces apoptosis, leading to destruction of the cell. The influx of granzymes into the cell can also be promoted by an endocytosis process mediated by the manose-6x`-phosphate receptor.
Functions of Treg Cells
Tregs are responsible for dampening the harmful activities of Th cells and fine-tuning immune responses. Moreover, they further have the ability to maintain homeostasis and prevent autoimmunity
Advantages of Treg Cell Therapies
Treg cell therapies can efficiently control or destroy various type of tumors and they are highly specific to target antigens in tumor cells. Treg therapies have minimal side effects as compared to the conventional treatments for oncological and autoimmune disorders.
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