FGL2-expressing Regulatory T Cells.
FGL2-expressing Regulatory T Cells.
| Molecule | CD8αα | CD8+CD45RClow | DNT cells | CD4+Foxp3+ |
|---|---|---|---|---|
| TCR | αβ, MHC-I/II restricted | αβ, MHC-I restricted | αβ, MHC-II restricted | αβ, MHC-II-restricted |
| Co-receptor | CD8αα
Small subset express CD4 or CD8 |
CD8αβ | Absent | CD4 |
| Origin | Lin-cells in intestinal epithelium, cryptopatches | Unknown | Thymus, periphery | Thymus |
| Development | Thymus (induced IEL from conventional T cells)
Thymus-independent |
CD40-Ig treatment | Thymus-dependent (DC+, IL-12+, IL-15), thymus-independent | Thymus (tTreg)
Induced in the periphery (pTreg) |
| Specificity | Self-antigen, foreign antigen, oligoclonal | Polyclonal | ||
| Markers | CD69, FasL, granzymes, CD122, B220, NK-Like receptors
Negative for CD2, CD5, CD28, LFA-1, mostly Thy1-negative |
CD45RClow, Foxp3, GITR, IL-10, and IL-13 | CD25, CD28, FasL, perforin, CTLA-4
Negative for NK1.1, Foxp3 |
CD25high, GITR, CTLA-4, OX-40, TIGIT, CD39/CD73, IL-35, PD-1, Gzmb |
| Cytokine expression | Low CD5 in intestine, TGF-β3, LAG-3, FGL2 | IFN-γ, IDO, FGL2 | FGL2, IFN-γ (not IL-2) | IL-10, TGF-β, FGL2 |
| Target cell/specialization | Homeostasis in intestine (food and microbes in lamina propria)
More common in the small intestine |
Interaction with plasmacytoid DC to suppress CD4+ T cell activity
Accumulated in the graft and spleen |
LPS-activated DC
CD8 and CD4 T cells Mature and immature DC B cells |
DC
T cells |
| Mechanisms | Inhibitory NK receptors CD8αα recruitment of LAT and LCK from the TCR | Contact-dependent- FGL2-mediated suppression of T cell proliferation
Contact-independent IDO-mediated suppression |
Trogocytosis and CD8+ T cell (FasL) mediated killing
CTLA-4 dependent downregulation of DC activation DC apoptosis through Fas:FasL |
DC inhibition by sequestration of CD80/CD86
T cell deprivation of IL-2 Inhibition of DC maturation Adenosine inhibition, impeding T cell effector and DC activity Anti-inflammatory Induction of apoptosis in target cells |
CTLA-4, cytotoxic T lymphocyte-associated protein 4; DC, dendritic cell; DNT, double negative T cell; FasL, fas ligand; FGL2, fibrinogen-like protein 2; Foxp3, forkhead box p3; GITR, glucocorticoid-induced TNFR family-related gene; Gzmb, granzyme B; IDO, indoleamine 2,3-deoxygenase; IEL, intraepithelial lymphocytes; IFN-γ, interferon gamma; Ig, immunoglobulin; IL, interleukin; LAG-3, lymphocyte activation gene 3; LAT, linker for activation of T cells; LCK, lymphocyte-specific protein tyrosine kinase; LFA-1, lymphocyte function-associated antigen 1; Lin, lineage; LPS, lipopolysaccharide; MHC, major histocompatibility complex; NK, natural killer; PD-1, programmed cell death-1; TCR, T cell receptor; TGF-β3, transforming growth factor beta 3; Thy1, thymocyte antigen; TIGIT, T cell immunoreceptor with Ig and ITIM domains.