Using interleukin (IL)-2 to preferentially expand regulatory T (Treg) cells constitutes an area of intense focus related to autoimmune disease. For example, providing low doses of IL-2 to patients with systemic lupus erythematosus (SLE) can increase the percentage of circulating Treg cells and may prove clinically beneficial. An initial study in which patients with SLE were given low-dose IL-2 reported an increase in the number of Treg cells, which was associated with an apparent decrease in a clinical SLE disease index (see {1}), suggesting that such an approach may warrant evaluation in future clinical trials. This study presented a similar IL-2 regimen in mice, which resulted in augmented programmed cell death 1 (PD-1) expression in an ‘activated-memory’ Treg cell subset, and PD-1 blockade resulted in apoptosis of these cells. Moreover, humans with graft-versus-host disease receiving low-dose IL-2 treatment could be retrospectively divided into likely responders and non-responders based on PD-1 expression on their peripheral Treg cells. This Recommendation is of an article referenced in an F1000 Faculty Review also written by Rosanne Spolski, Daniel Gromer, and Warren J. Leonard.