Table 1.
Overview of FoxP3− immune regulating T cells discussed in this review, how they are induced or activated, their main suppressive mechanism and how they function, their localization, animal models depletion assays, master genes for differentiation, and cell volume changes in complicated pregnancies.
| Subset | Induction/ activation | Suppressive mechanism | Function | Localization | Depletion in animal models | Master genes of differentiation | Cell volume changes in complications |
|---|---|---|---|---|---|---|---|
| CD4+HLA-G+ Treg (139, 160) | Natural occurring (139) | Secretion of sHLA-G and IL-10 (139), and cell interaction with HLA-G (160) | Induction of HLA-G expression by trophoblasts, DC-10s and Tregs by IL-10 Inhibition of macrophages, NK cells and T cell killing |
Found in peripheral blood (45) and decidua (141) | Has not been performed | Not known | Found to be increased in peripheral blood of pre-eclampsia patients (45) |
| Tr1-(like) Treg (109, 119) | Via trogocytosis (160) | Secretion of IL-10 and TGF-β, and cell interaction (136, 161) | Induction of HLA-G expression by trophoblasts, DC-10s and Tregs by IL-10 Lysis of APCs, disruption of metabolic state of T cells |
Found in peripheral blood and decidua (119) | Has not been performed | Not known | Has not been described |
| Th3 Treg (162) | By APC in an IL-10 dominant microenvironment (110) | Secretion of TGF-β and IL-10 (162) | Induction of HLA-G expression by trophoblasts, DC-10s and Tregs by IL-10 Inhibition of NK cell and T cells and APC by TGF-β |
Found in the decidua (163) | Has not been performed | Not known | Has not been described |
| CD8+ Treg (59) | By APC in presence of TGF-β and IL-4 (113, 135) | Suppress the secretion of immunoglobulins (164) | Prevent formation and suppressing production of IPA-specific antibodies. | Found in peripheral blood (CD8+HLA-G+ Treg) (45) and decidua (164) | Has not been performed | Not known | CD8+HLA-G+ Treg are increased in peripheral blood of pre-eclampsia patients (45) |
| NO-Treg (165) | CD101+CD103+ are induced by trophoblasts (164) | Secretion of IL-10 (165, 166) | Induction of HLA-G expression by trophoblasts, DC-10s and Tregs by IL-10. | Found in peripheral blood (165) | Has not been performed | Not known | Has not been described |
| TIGIT+ Treg (119) | Depends on nitric oxide, p53, IL-2, and OX-40 (165) | Secretion of IFNγ and IL-2 (119) | Induction of IL-10 production by APCs. Suppression of CD4+ effector T cells | Found in decidua (119) | Has not been performed | Not known | Has not been described |
| Vδ1+ γδ T cell (167) | Unknown | Secretion of IL-10 and TGF-β (115) | Induction of HLA-G expression by trophoblasts, DC-10s and Tregs by IL-10 Inhibition of NK cell and T cells and APC by TGF-β |
Found in peripheral blood and decidua (168) | Has not been performed | Not known | Decreased amount in an abortion prone mice model (111) |