The imbalance of CD4~+ CD25~+ Foxp3~(high) regulatory T cells/Thl7 cells in infant with sepsis
Objective To further explore the pathogenesis of disturbed adaptive immune response in infants with sepsis. Methods Forty-eight infants with sepsis and 26 age-matched healthy infants were enrolled in this study. The HLA-DR expression of CD14~+ monocyte, the proportion of CD4~+ CD25~+ Foxp3~(high) Tr cells and the proportion of Thl7 cells were measured by flow cytometry. Cytokines (IL-1β, IL-6, TNF-α, IL-10, TGF-β and IL-17A) were measured by ELISA. Real-time PCR were used to evaluate the mRNA levels of Foxp3, ROR-γt in CD4-positive cells and IL-17A. Forty-eight infants with sepsis were divided into two groups according to HLA-DR expression of CD14~+ monocyte: DR-H group ( ＞ 30% ) and DR-L group ( ＜ 30% ). Results The ratio of IL-10/TNF-α in DR-L group was higher than that in healthy control or DR-H group(P ＜0.05). The proportion of CD4~+ CD25~+ Foxp3~(high) Tr cells and mRNA expression of transcription factor Foxp3 in DR-L group was found to be significantly higher than that in healthy control or DR-H group(P＜0.05). The proportion of Thl7 cells, Serum concentration of IL-17A, the mRNA expression of IL-17A and transcription factor ROR-γt were significantly increased in DR-H group and DR-L group (P ＜ 0.05) , while there is no significant difference between DR-H and DR-L group( P ＞0.05). Serum levels of Th17-inducing cytokine such as IL-1β, IL-6 were significantly elevated in DR-H group and DR-L group (P＜0.05), while there is no significant difference between DR-H and DR-L group( P＞0.05). Serum level of CD4~+ CD25~+ Foxp3~(high) Tr-inducing cytokine TGF-p in DR-L group was higher than that in DR-H or healthy control group(P＜0. 05). Conclusion Over-activation of Th17 cells may be one of the factors causing aberrant increase of pro-inflammatory cytokine/chemotatic factor in infant with sepsis. The imbalance of CD4~+ CD25~+ Foxp3~(high) Tr cells/Th17 cells may be contributed to the pathogenic mechanism of mixed antagonist response syndrome ( MARS) in infant with sepsis. The changes of cytokine environment in infants with sepsis may be one of the factors causing the imbalance of CD4~+ CD25~+ Foxp3~(high) Tr cells/Th17 cells. 
 
Key words: 
Sepsis;  HLA-DR;  CD4~+ CD25~+ Foxp3~(high) regulatory T cells;  Thl7 cells;  Infant