Abstract
CD4+CD25+FOXP3+ regulatory T-cells (Tregs) form an important arm of the immune system responsible for suppressing untoward immune responses. Tregs can be thymically derived or peripherally induced, even from CD4+CD25-FOXP3- T-cells. FOXP3 expression and in vitro suppressive activity are considered unique hallmarks of this dedicated and stable lineage of regulatory cells. Here we show that virtually all human CD4+CD25-FOXP3- T-cells and CD8+CD25-FOXP3- T-cells attain a transient FOXP3+CD25+ state during activation. In this state of activation, these cells possess the classic phenotype of Tregs, in that they express similar markers and inhibit in vitro proliferation of autologous CD4+CD25- T-cells. This state is characterized by suppressed IFN-γ production and robust TNF-α and IL-10 production. Interestingly, the great majority of the activated cells eventually downregulate FOXP3 expression, with a concomitant drop in suppressive ability. Our results show that, in humans, FOXP3 expression and Treg functionality are not exclusive features of a stable or unique lineage of T-cells but may also be a transient state attained by almost all T-cells. These results warrant caution in interpreting human studies using FOXP3 and suppressive activity as readouts and suggest that attempts to induce "Tregs" may paradoxically result in induction of effector T-cells, unless stability is confirmed.
Original language | English |
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Pages (from-to) | 18-29 |
Number of pages | 12 |
Journal | Clinical Immunology |
Volume | 123 |
Issue number | 1 |
DOIs | |
State | Published - Apr 2007 |
Keywords
- CD4
- CD8
- FOXP3
- Human
- Regulatory T cells