Abstract
Regulatory T cells (Tregs) play a key role in the peripheral self-tolerance and preventing autoimmunity. While classical CD4(+) Foxp3(+) Tregs are well established, their CD8(+) counterparts are still controversial in many aspects including their phenotypic identity and their mechanisms of suppression.
Because of these controversies and because of only a limited number of studies documenting the immunoregulatory function of CD8(+) Tregs in vivo, the concept of CD8(+) Tregs is still not unanimously accepted. We propose that any T-cell subset considered as true regulatory must be distinguishable from other cell types and must suppress in vivo immune responses via a known mechanism.
In this article, we revisit the concept of CD8(+) Tregs by focusing on the characterization of individual CD8(+) T-cell subsets with proposed regulatory capacity separately. Therefore, we review the phenotype and function of CD8(+) FOXP3(+) T cells, CD8(+) CD122(+) T cells, CD8(+) CD28(low/-) T cells, CD8(+) CD45RC(low) T cells, T cells expressing CD8 alpha alpha homodimer and Qa-1-restricted CD8(+) T cells to show whether there is sufficient evidence to establish these subsets as bona fide Tregs.
Based on the intrinsic ability of CD8(+) Treg subsets to promote immune tolerance in animal models, we elaborate on their potential use in clinics.