Human anergic/suppressive CD4+CD25+ T cells: a highly differentiated and apoptosis‐prone population

LS Taams, J Smith, MH Rustin… - European journal of …, 2001 - Wiley Online Library
LS Taams, J Smith, MH Rustin, M Salmon, LW Poulter, AN Akbar
European journal of immunology, 2001Wiley Online Library
Abstract Anergic/suppressive CD4+ CD25+ T cells exist in animal models but their presence
has not yet been demonstrated in humans. We have identified and characterized a human
CD4+ CD25+ T cell subset, which constitutes 7–10% of CD4+ T cells in peripheral blood
and tonsil. These cells are a CD45RO+ CD45RBlow highly differentiated primedT cell
population that is anergic to stimulation. Depletion of this small subset from CD4+ T cells
significantly enhances proliferation by threefold in the remaining CD4+ CD25–T cells, while …
Abstract
Anergic/suppressive CD4+CD25+ T cells exist in animal models but their presence has not yet been demonstrated in humans. We have identified and characterized a human CD4+CD25+ T cell subset, which constitutes 7–10 % of CD4+ T cells in peripheral blood and tonsil. These cells are a CD45RO+CD45RBlow highly differentiated primedT cell population that is anergic to stimulation. Depletion of this small subset from CD4+ T cells significantly enhances proliferation by threefold in the remaining CD4+CD25 T cells, while the addition of isolated CD4+CD25+ T cells to CD4+CD25 T cells significantly inhibits proliferative activity. Blocking experiments suggest that suppression is not mediated via IL‐4, IL‐10 or TGF‐β and is cell‐contact dependent. Isolated CD4+CD25+ T cells are susceptible to apoptosis that is associated with low Bcl‐2 expression, but this death can be prevented by IL‐2 or fibroblast‐secreted IFN‐β. However, the anergic/suppressive state of these cells is maintained after cytokine rescue. These human regulatory cells are therefore a naturally occurring, highly suppressive, apoptosis‐prone population which are at a late stage of differentiation. Further studies into their role in normal and pathological situations in humans are clearly essential.
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