CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells

By Weihong Liu, A. Putnam, Xu-yu Zhou, G. Szot, Michael R. Lee, Shirley Zhu, P. Gottlieb, Philipp Kapranov, Thomas R. Gingeras, B. F. de St. Groth and 4 more. Journal of Experimental Medicine, 2006

2,743 citations recorded by the source corpus.

Regulatory T (T reg) cells are critical regulators of immune tolerance. Most T reg cells are defined based on expression of CD4, CD25, and the transcription factor, FoxP3. However, these markers have proven problematic for uniquely defining this specialized T cell subset in humans. We found that the IL-7 receptor (CD127) is down-regulated on a subset of CD4+ T cells in peripheral blood. We demonstrate that the majority of these cells are FoxP3+, including those that express low levels or no CD25. A combination of CD4, CD25, and CD127 resulted in a highly purified population of T reg cells accounting for significantly more cells that previously identified based on other cell surface markers. These cells were highly suppressive in functional suppressor assays. In fact, cells separated based solely on CD4 and CD127 expression were anergic and, although representing at least three times the number of cells (including both CD25+CD4+ and CD25−CD4+ T cell subsets), were as suppressive as the “classic” CD4+CD25hi T reg cell subset. Finally, we show that CD127 can be used to quantitate T reg cell subsets in individuals with type 1 diabetes supporting the use of CD127 as a biomarker for human T reg cells.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/4b3c9ad4dfcdfc61e9c392dc4b4b13ad39b9f028

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Citations in the corpus

Rapamycin Promotes Expansion of Functional CD4+CD25+FOXP3+ Regulatory T Cells of Both Healthy Subjects and Type 1 Diabetic Patients1 (2006, background): “Overall, these data indicate that there is no reduced frequency of CD4 CD25 FOXP3 Tregs in T1D subjects.”
Type 1 diabetes immunotherapy using polyclonal regulatory T cells (2015, background): “We have shown that a combination of cell surfacemarkers—CD4, CD25, andCD127—provides a robust cocktail to isolate FOXP3 Tregs by fluorescence-activated cell sorting (FACS) fromperipheral blood of subjects with T1D (19).”
Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression (2007, background): “Surface molecules linked to T reg cell suppression include CTLA-4 (9, 10), chemokine receptors (CCR4 and CCR8; reference 11), selectins (CD62L; reference 12), integrins (CD103; reference 13), and CD127 (14).”
Foxp3 instability leads to the generation of pathogenic memory T cells in vivo (2009, neutral): “In the pancreas of NOD mice, the balance was shifted from Foxp3 + T reg to exFoxp3 cells. exFoxp3 cells showed very high expression ofCD127, which is believed to be a direct Foxp3 target and represents a key marker of memory T cell subsets10,30.”
The PD-1 Pathway in Tolerance and Autoimmunity (2010, background): “Foxp3 interacts with the CD127 promoter and likely represses its protein expression, resulting in an inverse correlation between Foxp3 and CD127 expression (158, 159).”
Functional delineation and differentiation dynamics of human CD4+ T cells expressing the FoxP3 transcription factor. (2009, background): “The inability of Fr. III (CD45RA Foxp3lo cells) to suppress was confirmed by using CD127 as an additional marker for purifying FoxP3-expressing cells from CD4+ T cells (Figure S5; Liu et al., 2006; Seddiki et al., 2006).”