ABSTRACT
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.
ABSTRACT
Objective To study the change of CD4+ CD25+ Foxp3high regulatory T cells (Treg cells) and the molecules associated with Treg cells in different immune status in infant with sepsis, and to further clarity the pathogenesis of disturbed immune function in infant with sepsis. Method Totally 36 sepsis infants admitted in In-tensive Care Unit of Shenzhen Children' s Hospital from May 2007 to November 2007 and 16 age-matched healthy infants were collected for prospective study, after excluding autoimmune disease, immunodeficiency, inherited metabolic disorders, tumor, and drug-treatment that could affect immune function during lately 6 months. The study was approved by Ethics Committee of Shenzhen Children's Hospital. The 36 infants with sepsis were divided into two groups according to expression levels of HLA-DR in CD14-positive cells: DR-H group was defined as patients with HLA-DR > 30%, while DR-L group was defined as patients with HLA-DR < 30%. Expression levels of HLA-DR in CD14-positive cells and the proportion of Treg cells were analyzed by flow cytometry. Real-time PCR were used to evaluate the mRNA levels of Foxp3, CTLA-4,GITR, and IL-10 in CD4-posidve ceils. Statistical analysis was performed by one-way Anova. There was statistical difference with P < 0.05. Results The proportion of Treg cells in DR-L group was found to be significantly higher than that in healthy control or DR-H group (P <0.05).Compared with healthy control group or DR-H group, transcriptional levels of Foxp3, CTLA-4 and IL-10were significantly increased in DR-L group (P <0.05). The levels of GITR mRNA in DR-L group were detected to be higher than those in DR-H group (P < 0.05). Conclusions Aberrant increased proportion of Treg cells may be associated with suppressed immune status in infant with sepsis.