Treg Effector Molecules.
Treg Effector Molecules.
| Effector | Cell Type | Ligand/Receptor | Target Cell | Mechanism |
|---|---|---|---|---|
| CTLA-4 | Treg | B7 molecules (CD80/CD86) | DC | Inhibition of DC activation through the trans-endocytosis and degradation of CD80 and CD86 molecules by Treg
Sterically hinders the association of naïve T cells with DC through co-ordinated activity with LFA-1 Negative regulation of effector T cell survival by signaling through Foxp3 |
| IL-2 | Activated T cells | High-affinity IL-2 receptor | Treg | IL-2 deprivation by Treg in low-affinity TCR and antigen–MHC interactions induce T cell apoptosis |
| TIGIT | Treg, T cells, NK cells | CD155 (PVR), CD112 (PVRL2) | DC | Inhibition of IL-12 (p40) production by DCBinds CD155 (PVR) and CD112 (PVRL2) on APCs
Increases IL-10 expression inducing tolerogenic DC which suppress T cell proliferation and IFN-γ production |
| LAG-3 | Treg | MHC-II | DC | Inhibits DC maturation
Inhibits co-stimulation of naïve T cells by DC |
| CD39/CD73 | Activated Treg | Treg | Activated T cells, DC | CD39 converts ATP in the extracellular space into ADP and AMP, decreasing inflammation
CD39 increases suppressive activity of Treg CD73 converts AMP to adenosine which inhibits DC function and activated T cells |
| IL-10 | Treg | IL-10R | T cells, DC | Inhibits T cell proliferation, decreases production of IL-2, TNF-α, and IL-5
Impairs Th1 responses by inhibiting DC activation and inhibiting secretion of IL-2 |
| TGF-β | Treg | TGF-βR | T cells | Direct suppression of effector T cells
Inhibits cytokine production and cytotoxic function of T cells |
| IL-35 | Treg | IL-35R | Naïve T cells, DC | Direct inhibition of T cell proliferation
Induction of naïve T cells to become activated IL-35 Treg |
| Gzmb | Treg | Perforin-independent entry into target cell | Activated T cells, DC | Induction of apoptosis in target cells |
| FGL2 | T cells, Treg, activated Treg | FcγRIIB/RIII | DC | Inhibition of DC maturation
Suppression of Th1 and Th17 effector T cell responses |
ADP, adenosine diphosphate; AMP, adenosine monophosphate; APC, antigen-presenting cell; ATP, adenosine triphosphate; CTLA-4, cytotoxic T lymphocyte-associated protein 4; DC, dendritic cell; FGL2, fibrinogen-like protein 2; Foxp3, forkhead box p3; Gzmb, granzyme B; IL, interleukin; LAG-3, lymphocyte activation gene 3; LFA-1, lymphocyte function-associated antigen 1; MHC, major histocompatibility complex; PVR, poliovirus receptor; PVRL, poliovirus receptor ligand; TCR, T cell receptor; TGF, transforming growth factor; TIGIT, T cell immunoreceptor with Ig and ITIM domains.