Table 2.
Immunosuppressive and cytotoxic killing mechanisms used by CD8+ Treg subsets.
| Treg Subtype | Source/Origin | Key Markers | Organism | Functional Mechanisms | References |
|---|---|---|---|---|---|
| CD8+CD122+ | Thymus derived | CD122+
FoxP3+/- PD-1+ |
Mouse | Fas/FasL dependent killing IL-10 mediated suppression |
(134–136) |
| CD8+Foxp3+ |
Ex vivo induced (iTreg) Peripherally sourced (pTreg) |
FoxP3+
CD25+ Lag3+/- CTLA-4+ PD-1+/- GITR+/- CD28+/- CD107a+/- |
Mouse | +>- GzA/GzB dependent killing +>- perforin dependent killing Undefined contact-dependent suppression +>- CTLA-4 mediated suppression +<- IL-10 mediated suppression |
(27, 63, 137, 138) |
| Human | CCL4 mediated suppression +>- CTLA-4 mediated suppression +<- IL-35 mediated suppression +>- GzA/GzB dependent killing +>- perforin dependent killing |
(27, 63, 139, 140) | |||
| CD8+CD103+ |
Ex vivo induced (iTreg) Peripherally sourced (pTreg) |
CD103+
Foxp3+/- CD25neg CTLA-4neg GITRneg PD-1neg IL-10+ TFG-β+ |
Mouse | Undefined contact-dependent suppression +/- GzA/GzB dependent killing |
(141, 142) |
| Human | Undefined contact-dependent suppression +/- GzA/GzB dependent killing |
(27, 142, 143) | |||
| CD8αα+ IELs | Thymus derived | CD8αα+ CD8βneg
TCRαβ+ Foxp3neg CD44+ CD69+ CD103+ Lag3+ CTLA-4+ |
Mouse | +/- IL-10 mediated suppression +/- Fas/FasL dependent killing +/- GzA/GzB dependent killing +/- TRAIL/DR5 dependent killing +/- Perforin dependent killing |
(144–150) |
| CD4+CD8αα+ IELs | Peripherally sourced (pTreg) | CD4+CD8αα+ | Mouse | IL-10 mediated suppression Perforin dependent killing |
(151–153) |
| CD8+CD28neg | Peripherally sourced (pTreg) | CD28neg | Mouse | ILT3/ILT4 dependent killing | (154) |
| Human | GzA/GzB dependent killing granulysin dependent killing ILT3/ILT4 dependent killing |
(155–161) |
GzB, granzyme B; GzA, granzyme A; ILT3/ILT4, immunoglobulin-like transcripts 3 and 4; CCL4, chemokine (C-C motif) ligands 4; IEL, Intraepithelial lymphocytes.
Symbols: +/- pathway or marker is shown to be intermittently applicable or inconsistently reported between multiple studies. +>- pathways is most often shown to be applicable. +<- pathway is most often shown to be unnecessary of cell function.