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

Abstract

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.

• Authors: Aqeel Javeed, Baojun Zhang, Yanyan Qu, Aijun Zhang, Chenming Sun, Lianjun Zhang, Jun Liu, Chun Zeng, Yong Zhao
• Journal: Transplant immunology (Transpl Immunol) Vol. 20 Issue 4 Pg. 253-60 (Mar 2009) ISSN: 0966-3274 [Print] Netherlands
• PMID: 19146957 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• FOXP3 protein, human
• Forkhead Transcription Factors
• Interleukin-2 Receptor alpha Subunit
• Aspirin

Topics

• Animals
• Aspirin (administration & dosage)
• Cell Proliferation (drug effects)
• Cell Separation
• Dose-Response Relationship, Drug
• Female
• Flow Cytometry
• Forkhead Transcription Factors
• Immunophenotyping
• Immunosuppression Therapy
• Interleukin-2 Receptor alpha Subunit
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• T-Lymphocytes, Regulatory (drug effects, immunology, metabolism)
• Thymus Gland (drug effects, immunology, metabolism)