CD28− and CD28lowCD8+ Regulatory T Cells: Of Mice and Men

Abstract

Since the rebirth of regulatory (formerly known as suppressor) T cells in the early 1990s, research in the field of immune-regulation by various T cell populations has quickly gained momentum. While T cells expressing the transcription factor Foxp3 are currently in the spotlight, several other T cell populations endowed with potent immunomodulatory capacities have been identified in both the CD8+ and CD4+ compartment. The fundamental difference between CD4+ and CD8+ T cells in terms of antigen recognition suggests non-redundant, and perhaps complementary, functions of regulatory CD4+ and CD8+ T cells in immunoregulation. This emphasizes the importance and necessity of continuous research on both subpopulations of regulatory T cells (Tregs) so as to decipher their complex physiological relevance and possible synergy. Two distinct CD8-expressing Treg populations can be distinguished based on expression of the co-stimulatory receptor CD28. Here, we review the literature on these (at least in part) thymus-derived CD28low and peripherally induced CD28−CD8+ Tregs.

Homeostatic proliferation leads to telomere attrition and increased PD-1 expression after autologous hematopoietic SCT for systemic sclerosis

“…CD8 + CD28 − T-cells bear immunoregulatory properties [40], such as down-modulation of cytotoxic activity [41] and production of inhibitory soluble factors [42], and their numbers are usually found decreased in autoimmune diseases [43]. In type 1 diabetes (T1D) patients, increased CD8 + CD28 − cell frequencies after AHSCT may have contributed to hinder the autoimmune destruction of insulinproducing cells and to improve glycemic control [25].…”

Reparative T lymphocytes in organ injury

“…However, the interest in these cells has been relatively muted compared with that in CD4 + Tregs. Different CD8 + Treg subsets have been described, and there is growing evidence of their role in autoimmune diseases, cancer, and chronic infections (114)(115)(116).…”

Future prospects for CD8+ regulatory T cells in immune tolerance

“…In 2016, the presence of CD8 + CD28 low Treg cells in peripheral blood mononuclear cells (PBMCs) and in children's thymuses was described and also their thymic origin demonstrated. 9,116 CD8 + Tregs are associated with different phenotypes depending on the studies (CD122, CD28, CD45RC, CD103, PD-1) but mostly their phenotype is rather associated to a differentiation status of central memory cells or effectors memory as characterized by the absence of CD28, CD62L or CD122 expression. 3,117 Other teams describe them rather through the expression of CD44, CCR7 and CD62L which are markers of central memory cells 3,73 or CD122 + and CD28 + .…”