Ex Vivo Isolation and Characterization of Cd4+Cd25+ T Cells with Regulatory Properties from Human Blood

D Dieckmann, H Plottner, S Berchtold… - The Journal of …, 2001 - rupress.org
D Dieckmann, H Plottner, S Berchtold, T Berger, G Schuler
The Journal of experimental medicine, 2001rupress.org
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 …
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.
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