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 CD28^low and peripherally induced CD28^-CD8⁺ Tregs.

Keywords: CD8+ T-lymphocytes; human; immunoregulation; mouse; regulatory T cells; thymus; tolerance.

Figure 1

Summary of findings on CD8⁺CD28^low regulatory T cells (Tregs). In the thymus, T cell precursors will interact with stromal cells presenting antigens that are expressed under control of the transcription factor autoimmune regulator and differentiate into tTreg. In the periphery, these cells will enforce their regulatory function by secreting immunomodulatory cytokines and/or by inhibiting antigen-presenting cells. It cannot be excluded that CD8⁺CD28^low Treg can also differentiate, under specific tolerogenic conditions, in the periphery. So far, the immunosuppressive capacity of CD8⁺CD28^low Tregs has been documented in experimental models of multiple sclerosis, myasthenia gravis, and colitis. Solid lines indicate established features, and dashed lines indicate potential characteristics.