[Frontiers in Bioscience 16, 3004-3013, June 1, 2011]

Thymosin-alpha1 promotes the apoptosis of regulatory T cells and survival rate in septic mice

Jian Wan1,2, Yi Shan1,3, Hongwei Shan1, Guomin Li2, Tao Wang1, Jun Guan1, Xuefeng Liu1, Dechang Chen1, Wenfang Li1, Zhaofen Lin1

1Department of emergency and critical care medicine, Shanghai Changzheng Hospital, The Second Military Medical University, Shanghai, 200003, China, 2Department of intensive care unit, Jiangsu University affiliated Jintan Hospital, Jintan, Jiangsu Province, 213200, China, 3Department of emergency, the 306th Hospital of PLA, Beijing, 100101, China

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Materials and methods
3.1. Animal and grouping
3.2. Surgical procedure of CLP
3.3. Treatment for the THI group
3.4. Treatment for HC group
3.5. Survival rate
3.6. Sample collection
3.7. Flow cytometry
3.7.1. Measurement of CD4+CD25+Foxp3+ T lymphocytes
3.7.2. Measurement of apoptosis in CD4+CD25+ double-positive cells
3.8. Measurement of serum cytokines
3.9. Histological observation
3.10. Statistical analysis
4. Results
4.1. Survival rate
4.2. Flow Cytometry
4.2.1. The percentage of Tregs in CD4+ T lymphocytes
4.2.2. Apoptotic rate of CD4+CD25+ T lymphocytes
4.3. The change of serum cytokines
4.4. Histological observation
5. Discussion
6. Conclusion
7. Acknowledgements
8. References

1. ABSTRACT

Tregs are involved in immune disorder during sepsis; they can lead to a Th2 immune reaction. Their inhibitory effects can help alleviate inflammatory injury, but may also cause secondary immune inhibition. Thymosin-alpha1 is a polypeptide with powerful immunomodulatory activities. Current reports have shown that Thymosin-alpha1 conferred beneficial effects to septic patients. To explore the relationship between Thymosin-alpha1 and Tregs, in this study, we investigated the changing trend in CD4+CD25+Foxp3+ T lymphocytes in a CLP septic mouse model. We also investigated the variation of apoptotic rate of CD4+CD25+ T lymphocytes, cytokine variation, and change of model survival rate when Thymosin-alpha1 intervening or not. We observed that the 72-h survival rate was improved, the percentage of CD4+CD25+Foxp3+ T lymphocytes decreased and the apoptosis rate of CD4+CD25+ T lymphocytes increased after intervention of Thymosin-alpha1. At same time the expression of pro-inflammation cytokines IL-2, TNF-alpha and anti-inflammatory cytokines IL-10 and TGF-beta were regulated. In conclusion, Thymosin-alpha1 can effectively control the inflammatory response intensity and improve the 72-h survival rate of septic mice. Regulating Tregs may be another important role of Thymosin-alpha1 conditioning the immune reaction in sepsis.