Table 1.
Extracellular markers, transcription factors, and mechanisms of actions of various Treg subtypes.
Treg Subset | Origin | Markers | Transcription Factors | Suppressive Mechanism | References |
---|---|---|---|---|---|
tTregs | Generating in the thymus | CD4+, CD25hi, CD27lo, CTLA-4+, LAG-3+, TIGIT+, TIM-3+, PD-1+ | FOXP3pos | Cell-contact-dependent immunosuppression via receptors like CTLA-4 and PD-1 | [33] |
pTregs | Differentiating from peripheral naive CD4+ T cells | CD4+, CD25hi, CD27lo, CTLA-4+, LAG-3+, TIGIT+, Tim-3+, PD-1+ | FOXP3pos | Inhibitory function via soluble factors such as TGF-β1 and IL-10 | [33] |
Tr1 Tregs | Differentiating from peripheral naive CD4+ T cells | CD4+, CD25, CD49b+, LAG-3+ [3] | Tbet, Blimp-1, FOXP3neg [1] | Inhibitory function via IL-10 production | [34,35] |
Th3 Tregs | Differentiating from peripheral naive CD4+ T cells | CD4+, CD25+, CD69+, LAP+ | TGF-β, FOXP3neg | Inhibitory function via TGF-β production | [36] |
CD8+ Tregs | Differentiating from peripheral naive CD8+ T cells | CD8+, CD25+, CD122+, CD49d+ | FOXP3pos, Eomes, Helios, TGF-β | TGF-dependent control of Helios and homeostatic cytokine IL-15 [4] | [37,38] |
tTregs: thymus-derived Tregs, pTregs: peripherally derived Tregs, Tr1 Tregs: Type 1 Tregs, Th3 Tregs: T helper T cells, CTLA-4: Cytotoxic T-lymphocyte-associated protein 4, LAG-3: Lymphocyte-activation gene 3, TIGIT: T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains, TIM3: T-cell immunoglobulin and mucin domain-containing protein 3, PD-1: Programmed cell death protein 1, FOXP3: Forkhead box P3, TGF-β: Transforming Growth Factor β 1, IL-10: Interleukin-10, Tbet: T-box expressed in T cells, Blimp-1: B lymphocyte-induced maturation protein 1, LAP: Latency-associated peptide positive, Eomes: Eomesodermin, IL-15: Interleukin-15.