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. 2021 Dec 15;2(3):147–156. doi: 10.2478/rir-2021-0021

Table 2.

CD4+ Tregs markers and mechanisms of action.

Subset Natural/induced Markers Mechanisms of Action Ref.
CD4+ Tregs (mice, humans) Induced/natural CD4, CD25, FoxP3, IL-10, IL-35, GITR, CD127low Suppress T effector cells, cell-to-cell contact, downregulation of CD80/CD86, metabolic disruption [18, 40, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75]
CD4+ Tregs (humans) Natural CD4, CD25, GARP, CD45RA/RO, CCR6 Helios, CD127low Suppress T effector cells [35, 40, 46, 47, 63, 76, 77, 78]
Tr1 Natural CD4, CD25, IL-10, IL-35 Suppress T effector cells, induction of B7-H4 on APCs through IL-10, TGF-β, IL-35 [40, 46, 47, 79]
Th1, Th2, Th3 Natural CD4, CD25, CXCR CXCR3+ T cells that can produce IFN-γ, IL-4 Suppress T effector cells through IL-10, TGF-β, IFN-γ, IL-4 [63, 64, 65, 66, 67]
IL-17+ FoxP3+ Tregs (mice, humans) Natural CD4, FOXP3, CCR6, RORγt Suppress CD4+ T cell proliferation [40, 46, 47]
CD45RA+ FoxP3low Tregs (mice, humans) Natural CD4, CD45RA, FOXP3 Resting Tregs [40, 46, 47]
Follicular Tregs (mice) Natural CD4, Foxp3, CXCR5, Bcl6 Germinal centers [40, 46, 47]
CD4+CD25low/−GITR+ (humans) Natural CD4+ CD25low/−GITR+ Suppress T effector cells [48]
CD4+CD25+ CXCR2+FoxP3+ CD45RO+ (humans) Natural/induced CD4+CD25+ CXCR2+FoxP3+ CD45RO+ Suppress T effector cells [51]
CD4+CD161+ FoxP3+ (humans) Natural CD127low, IL-2, IFNγ, IL-17 Suppress T effector cells [57, 58]
CD4+CXCR5+ FoxP3+ (mice, humans) Natural CD4+CXCR5+ Suppress B-cell antibody production [59]
Follicular CD4+Bcl6FoxP3+ Tregs (mice, humans) Natural CD4+Bcl6FoxP3+ Suppress germinal center reactions [60]

APC, antigen presenting cells; Tregs, T regulatory cells; Tr1, type-1 regulatory.