Abstract
In central lymphoid tissues, mature lymphocytes are generated and pathogenic autoreactive lymphocytes are deleted. However, it is currently known that a significant number of potentially pathogenic autoreactive lymphocytes escape the deletion and populate peripheral lymphoid tissues. Therefore, peripheral mechanisms are present to prevent these potentially pathogenic autoreactive lymphocytes from harming one’s own tissues. One such mechanism is dictated by regulatory T (Treg) cells. So far, the most extensively studied Treg cells are CD4+Foxp3+ Treg cells. However, recent clinical trials for the treatment of immune-mediated diseases using CD4+ Foxp3+ Treg cells met with limited success. Accordingly, it is necessary to explore the potential importance of other Treg cells such as CD8+ Treg cells. In this regard, one extensively studied CD8+ Treg cell subset is Qa-1(HLA-E in human)-restricted CD8+ Treg cells, in which Qa-1(HLA-E) molecules belong to a group of non-classical major histocompatibility complex Ib molecules. This review will first summarize the evidence for the presence of Qa-1-restricted CD8+ Treg cells and their regulatory mechanisms. Major discussions will then focus on the potential clinical translation of Qa-1-restricted CD8+ Treg cells. At the end, we will briefly discuss the current status of human studies on HLA-E-restricted CD8+ Treg cells as well as potential future directions.
Highlights
Adaptive immune system is composed of central lymphoid tissues and peripheral lymphoid tissues
In the central lymphoid tissues, lymphocytes obtain the ability to react to foreign proteins while those lymphocytes that are capable of reacting to self-proteins and harming self-tissues are deleted
We have proposed that these unique features endow Qa-1(HLA-E)-restricted CD8+ Treg cells with the ability to regulate activated cells [37]
Summary
Adaptive immune system is composed of central lymphoid tissues and peripheral lymphoid tissues. CD8+ T cells infiltrating the tissues where autoimmune diseases occur were not pathogenic and played a regulatory role [3,27] In this regard, CD8+ Treg cells were first described in 1970s [28]. Among various subsets of CD8+ Treg cells, CD8+ Treg cell subset, restricted by Qa-1(HLA-E in human) molecules, is the most extensively characterized CD8+ Treg cells because of its well-defined immune regulatory role [37,38,39,40]. We believe that, based on the solid evidence on their immune regulatory role as described Qa-1(HLA-E)-restricted CD8+ Treg cells should be considered as potential therapies for human diseases. Further investigations into the importance of these unique features are justified
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