CD4+ CD25+ Treg

Markers: CD4+, CD25+, CD62L+, CTLA-4+, FoxP3+

MHC-II-presented polysaccharide A (PSA) and possibly other T cell-dependent polysaccharides are recognized explicitly by CD4+ T cells with regulatory T cell activity
Johnson et al. 2015a Journal of Biological Chemistry 290: 5007-5014

CD4+ CD25++ FOXP3 low nTreg / tTreg and CD4+ CD25+ FOXP3 high Treg (peripherally induced) both express forkhead box protein 3 (FoxP3). Neuropilin-1 and Helios are typically found on thymus-derived regulatory T cells (tTregs) and are frequently used as markers to differentiate them.
Thornton et al. 2010 J Immunol 184(7): 3433-3441
Yadav et al. 2012 J Exp Med 209(10): 1713-1722

Helios is also expressed on CD4+ CD25+ FOXP3 high Treg (peripherally induced), making these markers imperfect.
Akimova et al. 2011 PLoS One 6(8): e24226
Gottschalk et al. 2012 J Immunol 188(3): 976-980

Insulin-like growth factor-binding protein 7 (IGFBP7)(?id=019d83cf-d5a5-49b6-98c7-49af01932cdd&linkText=Insulin-like+growth+factor-binding+protein+7+%28IGFBP7%29), galectin-1, granzyme B, and ikzf 2 gene (wild-type)(?id=92e9beb7-294e-4ec3-9ba2-7988718cfda0&linkText=Helios) are found to be specifically expressed in CD4+ CD25++ FOXP3 low nTreg / tTreg, but independent of Foxp3 expression
Ohkura et al., 2010

Multiple mechanisms including cell contact and factor-mediated ones may operate in Treg-mediated suppression (Immunosuppression). CD4+ CD25 + Treg cells require antigen stimulation via TCR to exert Treg suppressive function in vitro
Ohkura et al., 2010

Expression of Foxp3 / FOXP3 / Scurfin at low levels induces a limited CD4+ CD25+ Regulatory T Cells (Tregs) phenotype but not suppressive function, which is only gained when FOXP3 is highly expressed
Sakaguchi et al. 2010 Nature 10: 490

Treg-mediated suppression involves secretion of suppressive humoral factors, such as IL-10 , Transforming growth factor beta (TGF-beta) , IL-35 , and galectin-1
Tang & Bluestone 2008 Nat Immunol 9(3): 239-244
Vignali et al. 2008 Nat Rev Immunol 8(7): 523-532
Shevach 2009 Immunity 30(5): 636-645

Contact-mediated suppression by CD4+ CD25+ regulatory cells involves a granzyme B-dependent, Perforin / Perforin-1-independent mechanism
Gondek et al. 2005 J. Immunol. 174: 1783-1786

CD4+ CD25+ Treg suppress tumor-specific CD8 T cell cytotoxicity through Transforming growth factor beta (TGF-beta) signals in vivo
Chen et al. 2005 Nucleic Acids Res. 33: D325–D328

CD4+ CD25+ Treg inhibit other T cells by T cell–to–T cell interaction
Scotto et al. 2004

In addition to characteristic expression of cell surface molecules such as CD25, CD4+ CD25++ FOXP3 low nTreg / tTreg cells specifically express the transcription factor Foxp3
Fontenot et al. 2003 Nat Immunol 4(4): 330-336
Hori et al. 2003 Science 299: 1057-1061
Khattri et al. 2003 Nat. Immunol 4: 337-342

CD4+ CD25+ Treg suppress immune responses in vitro and in vivo. One of the best characterized subsets of Treg is expression of a chain of IL-2R (CD25)
Roncarolo et al., 2001

CD4+ CD25+ Treg down-regulate co-stimulatory molecules on APCs (antigen presenting cells)
Cederbom et al. 2000 Eur J Immunol 30: 1538-1543

CD4+ CD25+ Treg suppress CD4+ by Interleukin-10 (IL-10), Transforming growth factor beta (TGF-beta) secretion
Ciubotariu et al. 1998

see also:
Zinc Finger Protein Helios (IKFZ2)+ Foxp3+ Colonic Treg cells