The significantly enhanced frequency of functional CD4⁺CD25⁺Foxp3⁺ T regulatory cells in therapeutic dose aspirin-treated mice

CD4⁺CD25⁺Foxp3⁺ regulatory T (Treg) cells, produced in the thymus or periphery as a functionally mature T cell subpopulation, play pivotal roles in maintenance of self-tolerance and negative regulation of immune responses. Aspirin (ASA) is widely used to reduce pain, the risk of cardiovascular diseases and allo-graft rejection. However, the effect of ASA on CD4⁺CD25⁺Foxp3⁺ Treg cells has yet to be determined. The frequency, phenotype and immunosuppressive function of CD4⁺CD25⁺Foxp3⁺ Treg cells were detected in BALB/c mice treated with low or high doses of ASA for 4 weeks. ASA significantly decreased the percentage and number of CD4⁺ T cells in the periphery, while ASA remarkably increased the percentage of CD4⁺CD25⁺Foxp3⁺ Treg cells in CD4⁺T cells. The total cell numbers of thymocytes were significantly decreased in ASA-treated mice, but the number of CD4⁺ CD25⁺Fxop3⁺ cells and its ratio in CD4⁺CD8^- thymocytes were markedly enhanced in the thymi of ASA-treated mice. The phenotype of CD4⁺CD25⁺ Treg cells, including the expressions of CD44, CD45RB, CD62L, CD69, GITR and CTLA-4, did not show detectable changes in ASA-treated mice. CD4⁺CD25⁺ Treg cells in ASA-treated mice exhibited unimpaired immunosuppressive function on CD4⁺CD25^- T effector cells. ASA significantly enhanced the frequency of functional CD4⁺CD25⁺Foxp3⁺ Treg cells in mice in a therapeutic dose range. The different effects of ASA on CD4⁺CD25⁺Foxp3⁺ Treg cells and CD4⁺CD25^- T cells may potentially make hosts susceptible to tolerance induction which would be beneficial for tolerance induction in patients with autoimmune diseases or allo-grafts. This study may have potential impacts in the clinical application of ASA.