Regulatory T Cells: Promises and Challenges
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IMMUNOLOGY (R FAIRCHILD, SECTION EDITOR)
Regulatory T Cells: Promises and Challenges Juliano AlHaddad 1
&
Gandolina Melhem 1 & Hazim Allos 1 & Jamil Azzi 1
# Springer Nature Switzerland AG 2020
Abstract Purpose of Review Soon after their discovery in 1972, regulatory T cells (Tregs) appeared as nature’s gift to induce tolerance in auto- and alloimmune settings. We review here the barriers to the use of these bona fide cells and the strategies implanted to overcome them. Recent Findings Tregs are extremely rare and heterogenous, rendering them difficult to isolate and expand in vitro. Furthermore, their adoptive transfer was hurdled by their phenotypic instability and lack of intrinsic survival signals. Most studies in the field have focused on identifying distinctive Tregs markers for their pure isolation. This has also led to the discovery of different subtypes within this regulatory population, such as TR1 cells and CD8 + Tregs. In parallel, a myriad of techniques has been implanted for the targeted delivery of IL-2 as well as the bioengineering of Tregs with antigen-specific chimeric antigen receptors. Summary Despite the drawbacks of the use of Tregs, strategies based on targeted delivery of IL-2 and hijacking conventional CD4 cells into suppressive cells are emerging as a promising tool in the field of transplantation. However, more studies are still required, as the long-term safety and stability of these bioengineered cells remain under investigation. Keywords Regulatory T cells . Tolerance . Interleukin-2 . Chimeric antigen receptor . CD8 + regulatory T cells . Type 1 regulatory cells
Introduction Immune responses involve a dynamic and tightly regulated interplay between a vast sum of distinct physiological actors. With any lapses in this balance, the immune system can fail to provide adequate protection to its host or, conversely, can trigger uncontrollable responses against nonpathogenic substances and/or self-antigens, resulting in boisterous autoimmunity. The adaptive immune systems’ major suppressive agent, the regulatory T cell, or Treg, has recently been implicated to play a crucial role in downregulating major immune responses and mediating this fine homeostasis [1].
Juliano AlHaddad and Gandolina Melhem contributed equally to this work. This article is part of the Topical Collection on Immunology * Jamil Azzi [email protected] 1
Transplantation Research Center, Renal Division, Brigham and Women’s Hospital , Harvard Medical School, 221 Longwood Ave, Boston, MA 02115, USA
Gershon et al. were the first group to present evidence for the existence of a subset of T cell that harbors immunosuppressive capabilities. Since then, the quest for this holy grail of immune regulation has divided the field into believers and skeptics. This groundbreaking study was the first to identify that certain T cells, or possibly their by-products, were able to interfere with effector T cell responses, suggesting a role in immunological tolerance or general feedback regulation [2]. Subsequent studies confirmed
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