Low-dose IL-2 for in vivo expansion of CD4⁺ and CD8⁺ regulatory T cells in nonhuman primates

IL-2 is a known potent T cell growth factor that amplifies lymphocyte responses in vivo. This capacity has led to the use of high-dose IL-2 to enhance T cell immunity in patients with AIDS or cancer. However, more recent studies have indicated that IL-2 is also critical for the development and peripheral expansion of regulatory T cells (Tregs). In the current study, low-dose IL-2 (1 million IU/m² BSA/day) was administered to expand Tregs in vivo in naïve nonhuman primates. Our study demonstrated that low-dose IL-2 therapy significantly expanded peripheral blood CD4⁺ and CD8⁺ Tregs in vivo with limited expansion of non-Treg cells. These expanded Tregs are mainly CD45RA^- Foxp3 ^high activated Tregs and demonstrated potent immunosuppressive function in vitro. The results of this preclinical study can serve as a basis to develop Treg immunotherapy, which has significant therapeutic potential in organ/cellular transplantation. Low-dose IL-2 therapy significantly expands functional CD4⁺ and CD8 ⁺ regulatory T cells in the peripheral blood with limited expansion of non-Treg cells in nonhuman primates.