Future prospects for CD8+ regulatory T cells in immune tolerance

Abstract

CD8⁺ Tregs have been long described and significant progresses have been made about their phenotype, their functional mechanisms, and their suppressive ability compared to conventional CD4⁺ Tregs. They are now at the dawn of their clinical use. In this review, we will summarize their phenotypic characteristics, their mechanisms of action, the similarities, differences and synergies between CD8⁺ and CD4⁺ Tregs, and we will discuss the biology, development and induction of CD8⁺ Tregs, their manufacturing for clinical use, considering open questions/uncertainties and future technically accessible improvements notably through genetic modifications.

Keywords: CD8+ Treg; therapy; tolerance.

Figure 1

Schematic depicting identified mechanisms of action and markers of rat, mouse and human CD8⁺CD45RC^low/- Tregs. Breg, regulatory B cell; Co‐stim, costimulatory molecules; DC, dendritic cell; EC, endothelial cell; IDO, indoleamine 2,3‐dioxygenase; Kyn, kynurenin; Mreg, regulatory macrophages; pDC, plasmacytoid dendritic cell; Trp, tryptophan. Bended arrows indicate conversion or induction. Up and down arrows indicate increase and decrease, respectively

Figure 2

CD8⁺ Treg‐based therapy process. In vitro steps are indicated in pink background, optional steps in blank background and clinical steps in blue background. CNI, calcineurin inhibitor; KI, knock‐in; KO, knock‐out; MMF, mycophenolate mofetil; Prdn, prednisolone; TAC, tacrolimus; UCB, umbilical cord blood