Partial depletion of CD69low-expressing natural regulatory T cells with the anti-CD25 monoclonal antibody PC61.

The role CD4(+) CD25(+) regulatory T cells (Treg) play in modulating the immune response has been investigated extensively over recent years. Much of the work to date has used the activation marker CD25 to define, enrich and deplete Treg. However, the identification of FoxP3 as a definitive marker of Treg has allowed us to study the effect of monoclonal antibodies against CD25 on regulatory T-cell populations. Recently, published data have indicated that Treg are inactivated, not depleted, through treatment with anti-CD25 monoclonal antibody. Using FoxP3-Green fluorescent protein reporter mice, we show that treatment with the CD25 MoAb PC61 depleted a subpopulation of Treg. The depleted Treg population expressed low levels of the CD69 marker, indicating an inactive phenotype. In addition, PC61 treatment altered the function of the remaining regulatory T-cell population, preventing their ability to modulate autoimmune diseases. Thus, our results have important implications with regard to interpreting experimental outcomes from in vivo anti-CD25 treatments.