Ex Vivo Isolation and Characterization of Cd4+Cd25+ T Cells with Regulatory Properties from Human Blood
By D. Dieckmann, Heidi Plottner, S. Berchtold, T. Berger, Gerold Schuler. Journal of Experimental Medicine, 2001
1,278 citations recorded by the source corpus.
It has been known for years that rodents harbor a unique population of CD4+CD25+ “professional” regulatory/suppressor T cells that is crucial for the prevention of spontaneous autoimmune diseases. Here we demonstrate that CD4+CD25+CD45RO+ T cells (mean 6% of CD4+ T cells) are present in the blood of adult healthy volunteers. In contrast to previous reports, these CD4+CD25+ T cells do not constitute conventional memory cells but rather regulatory cells exhibiting properties identical to their rodent counterparts. Cytotoxic T lymphocyte–associated antigen (CTLA)-4 (CD152), for example, which is essential for the in vivo suppressive activity of CD4+CD25+ T cells, was constitutively expressed, and remained strongly upregulated after stimulation. The cells were nonproliferative to stimulation via their T cell receptor for antigen, but the anergic state was partially reversed by interleukin (IL)-2 and IL-15. Upon stimulation with allogeneic (but not syngeneic) mature dendritic cells or platebound anti-CD3 plus anti-CD28 the CD4+CD25+ T cells released IL-10, and in coculture experiments suppressed the activation and proliferation of CD4+ and CD8+ T cells. Suppression proved IL-10 independent, yet contact dependent as in the mouse. The identification of regulatory CD4+CD25+ T cells has important implications for the study of tolerance in man, notably in the context of autoimmunity, transplantation, and cancer.
Subfields: Immunology
View Paper: https://www.semanticscholar.org/paper/8a231dc6aa56803ffc949f56b6ab9ab0a18bd650
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Citations in the corpus
- Prevalence of Regulatory T Cells Is Increased in Peripheral Blood and Tumor Microenvironment of Patients with Pancreas or Breast Adenocarcinoma1 (2002, background): “Treg have been isolated from human PBMCs (2) and mouse spleen (3).”
- CD25+CD4+ Regulatory T Cells Prevent Graft Rejection: CTLA-4- and IL-10-Dependent Immunoregulation of Alloresponses1 (2002, background): “Given our data regarding CD122 expression, it is interesting to note that CD122 has recently been shown to be constitutively expressed on ex vivo isolated human regulatory CD25 CD4 T cells (44, 45).”
- Foxp3 Expressing CD4+CD25high Regulatory T Cells Are Overrepresented in Human Metastatic Melanoma Lymph Nodes and Inhibit the Function of Infiltrating T Cells1 (2004, background): “Indeed, in human PBMCs, we found that Foxp3 is expressed almost exclusively by the CD4 CD25 T cell population that is known to contain Treg (27, 28, 30, 31).”