Recent advances in CD8+ regulatory T�cell research (Review)

Abstract

Various subgroups of CD8 T lymphocytes do not only demonstrate cytotoxic effects, but also serve important regulatory roles in the body's immune response. In particular, CD8 regulatory T cells (CD8 Tregs), which possess important immunosuppressive functions, are able to effectively block the overreacting immune response and maintain the body's immune homeostasis. In recent years, studies have identified a small set of special CD8 Tregs that can recognize major histocompatibility complex class Ib molecules, more specifically Qa-1 in mice and HLA-E in humans, and target the self-reactive CD4 T ce lls. These findings have generated broad implications in the scientific community and attracted general interest to CD8 Tregs. The present study reviews the recent research progress on CD8 Tregs, including their origin, functional classification, molecular markers and underlying mechanisms of action.

Exosomes transmit retroelement RNAs to drive inflammation and immunosuppression in Ewing Sarcoma

“…Respective HERV-K and HSAT2-positive cell populations were significantly expanded in the peripheral blood of EwS patients compared to healthy donors. These populations exhibited phenotypic features of MDSCs (CD33 + HLA-DR -, CD33 + CD25 + , CD33 + PD1 + ) 11,33,37 and of exhausted or regulatory CD8 + T-cells (CD8 + CD25 + PD-1 + ) 13,35 . EwS-derived RNAs may thus co-opt key cell populations of the innate and adaptive immune system, skewing them towards immunosuppressive phenotypes.…”

“…Surprisingly however, the CD8 + subsets, such as HSAT2-positive CD25 -PD-1 + and CD25 + PD-1as well as CD25 + PD-1 + (positive for both HSAT2 and HERV-Kpol), were also identified in healthy donors (Fig. 3b, top panels), likely reflecting their involvement in surveillance or tolerance to self-antigens 35 . These subsets, however, were significantly expanded in EwS patients, representing only ~1-2% of total CD8 + T-cell population in healthy donors and up to 15% in patients (p<0.005, Wilcoxon test; Fig.…”

“…Meanwhile, CD45 + CD3 + CD4 + T-cells and CD45 + CD19 + B-cells were consistently negative ( To further characterize HERV-Kpol and HSAT2-positive populations, we employed HLA-DR (differentiation marker, to distinguish between more differentiated HLA-DR + myeloid cells and HLA-DR -MDSCs) 11,33 , CD25 (CD8 + T-cell activation marker; also associated with MDSCs or with immunosuppressive regulatory CD4 + and CD8 + T-cells) 12,14 and PD-1, one of the best characterized markers of tolerance, immunosuppression and CD8 + T-cell exhaustion 13,14 . Analysis of PBMCs from an additional 5 patients (all with localized tumors; pre-treatment) and 5 healthy donors identified the largest subsets positive for both HERV-Kpol and HSAT2, including CD33 + HLA-DR -(early-stage MDSCs 33 ), CD33 + PD-1 + and CD33 + CD25 + MDSC-like cells, and CD8 + CD25 + PD-1 + T-cells with exhaustionassociated phenotype 13,14,35 (Fig. 3b, top panels).…”

Regulatory T cells and co‐evolution of allele‐specific MHC recognition by the TCR

“…In the periphery, antigen stimulation and innate immune inflammatory responses can induce conventional CD4+ T cells to become peripheral CD4+CD25+ FoxP3+ pTregs [38][39][40][41] and more importantly it is now clear that induced pTregs play important roles in both Germinal Centre formation and the regulation of such sites of B lymphocyte hypermutation, memory formation and affinity/avidity maturation. [42][43][44][45] Of more importance for our argument, here is the accumulating evidence for a key role of induced peripheral CD8+ Tregs in the Germinal Centre reaction itself.…”

Synthesis of peptide conjugates with vitamins for induction of antigen‐specific immunotolerance

“…T reg cells expressing CD4 (CD4 + T reg ) compete with helper T cells to induce immunotolerance, whereas T reg cells expressing CD8 (CD8 + T reg ) aid induction of immunotolerance by several pathways including secretion of cytokines. [4][5][6][7] Induction of tDC is facilitated by small molecules such as vitamins and rapamycin. 8,9 For efficient induction of antigen-specific immunotolerance, nanoparticle formulations containing both antigens and tDC-inducing molecules have been reported.…”