Abstract
T regulatory cell therapy presents a novel therapeutic strategy for patients with autoimmune diseases or who are undergoing transplantation. At present, the CD4+ Treg population has been extensively characterized, as a result of defined phenotypic and functional readouts. In this review article, we discuss the development and biology of CD8+ Tregs and their role in murine and human disease indications. A subset of CD8+ Tregs that lack the surface expression of CD28 (CD8+CD28− Treg) has proved efficacious in preclinical models. CD8+CD28− Tregs are present in healthy individuals, but their impaired functionality in disease renders them less effective in mediating immunosuppression. We primarily focus on harnessing CD8+ Treg cell therapy in the clinic to support current treatment for patients with autoimmune or inflammatory conditions.
Highlights
The immune system is a comprehensive network of multifaceted cells that exert an array of systemic and tissue-dependent functionalities
We have previously shown that, in rheumatoid arthritis (RA) patients, CD8+ CD28− T regulatory cells (Tregs) are dysfunctional due to defective suppressor function and/or the reduced responsiveness of target cells to suppression, which can be corrected by anti-TNF therapy [33]
We have shown that CD8+ CD28− Tregs are significantly increased numerically in the peripheral blood (PB) of RA patients treated with methotrexate (RA(MTX))
Summary
The immune system is a comprehensive network of multifaceted cells that exert an array of systemic and tissue-dependent functionalities. CD4+ Tregs has evolved to include a relatively small set of phenotypic and functional markers such as the expression of Foxp, CD127− /low and helios and inhibitory cytokine production: IL-10, IL-35 and transforming growth factor beta (TGF-β1). A vast array of markers and functions have been reported for CD8+ suppressor cells ( referred to as CD8+ Tregs) in mouse and human studies. Human placental trophoblasts can activate CD8+ Tregs [12] and, in the eye, ocular pigment epithelial cells can covert CD8+ T cells to CD8+ CD25+ Foxp3+ Tregs [13] This demonstrates that CD8+ Tregs can mediate suppression in immune privilege sites. We have previously shown that, in RA patients, CD8+ CD28− Tregs are dysfunctional due to defective suppressor function and/or the reduced responsiveness of target cells to suppression, which can be corrected by anti-TNF therapy [33].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
