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.