Expression of interleukin (IL)-2 and IL-7 receptors discriminates between human regulatory and activated T cells

By N. Seddiki, B. Santner‐Nanan, J. Martinson, J. Zaunders, S. Sasson, A. Landay, Michael Solomon, W. Selby, S. Alexander, R. Nanan and 2 more. Journal of Experimental Medicine, 2006

1,648 citations recorded by the source corpus.

Abnormalities in CD4+CD25+Foxp3+ regulatory T (T reg) cells have been implicated in susceptibility to allergic, autoimmune, and immunoinflammatory conditions. However, phenotypic and functional assessment of human T reg cells has been hampered by difficulty in distinguishing between CD25-expressing activated and regulatory T cells. Here, we show that expression of CD127, the α chain of the interleukin-7 receptor, allows an unambiguous flow cytometry–based distinction to be made between CD127lo T reg cells and CD127hi conventional T cells within the CD25+CD45RO+RA− effector/memory and CD45RA+RO− naive compartments in peripheral blood and lymph node. In healthy volunteers, peripheral blood CD25+CD127lo cells comprised 6.35 ± 0.26% of CD4+ T cells, of which 2.05 ± 0.14% expressed the naive subset marker CD45RA. Expression of FoxP3 protein and the CD127lo phenotype were highly correlated within the CD4+CD25+ population. Moreover, both effector/memory and naive CD25+CD127lo cells manifested suppressive activity in vitro, whereas CD25+CD127hi cells did not. Cell surface expression of CD127 therefore allows accurate estimation of T reg cell numbers and isolation of pure populations for in vitro studies and should contribute to our understanding of regulatory abnormalities in immunopathic diseases.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/dae73fdd18680742d2c1b03549de4d04fd103a8a

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Citations in the corpus

The PD-1 Pathway in Tolerance and Autoimmunity (2010, background): “represented a more pure population of regulatory cells that were more suppressive than their CD4CD25CD127 counterparts (158, 160).”
Functional delineation and differentiation dynamics of human CD4+ T cells expressing the FoxP3 transcription factor. (2009, methodology): “III (CD45RA Foxp3 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).”
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.”
Immunosenescence of ageing (2007, background): “Recently, the observation that the IL-7 receptor (CD127) is not expressed on Foxp3+ cells and a subset of CD4+, CD25+, CD127 cells are suppressive, but CD127 cells are not, indicates that this may be a useful staining protocol to identify live Tregs in functional assays [115,116].”
OMIP-042: 21-color flow cytometry to comprehensively immunophenotype major lymphocyte and myeloid subsets in human peripheral blood (2017, background): “Of note, HLADR and CD38 expression identifies T cell activation status within any subset (10), with an example shown for all CD41 cells.”
Activation-induced FOXP3 in human T effector cells does not suppress proliferation or cytokine production. (2007, background): “Recently, it was reported that human nTregs can be distinguished from Teff cells on the basis of low CD127 (IL-7Ra) expression (26, 27 ), possibly due to the capacity of FOXP3 to interact with and repress the CD127 promoter (26).”
New insights into the regulation of T cells by γc family cytokines (2009, neutral): “Similarly, most human CD4 + CD25 + FOXP3 + T Reg cells have lower levels of IL-7Rα expression than do CD4 + CD25 + FOXP3 − T cell”