Study On The Expression And Function Of Regulatory T Cells In Senile Pneumonia

Purpose: Senior individuals(adults older than the age of 65)are particular at risk of developing pneumonia,often with more severe symptoms and faster progression.The pathogenesis is not entirely clear.It is known that environmental insults such as air pollutions possibly cause cumulative damages to the airways and the lung tissue and compromise the defense against incoming pathogens.Recent studies have shown that senior individuals tend to display a dysregulated immune system with both quantitative declines and qualitative alterations.These conditions might prevent effective clearance of pathogens in the lung and allow disease progression in senior individuals.Regulatory T cell(Treg)is an important part in human immune system,and plays critical roles in suppressing inflammatory responses.The purpose of this study was to investigate changes of Treg in senior pneumonia patients.Materials and methods: Fifteen senior adults with community-acquired bacterial pneumonia and 15 sex and age-match healthy controls were recruited for this study.Peripheral blood was collected on each subject.The characteristic transcription factors,Foxp3 and Helios,for Tregs were examined by flow cytometry.The transcriptional level of cytokines was examined by q PCR.The secretion of anti-inflammatory cytokines and cytotoxic factors was examined by ELISA.The roles of Tregs on effector cells were examined by cell co-culture experiments in vitro.In addition,pneumonia severity index(PSI)was compared with Treg parameters.Results: The proportion of Foxp3+Tregs in CD4+T cells was significantly decreased in senior pneumonia patients than in healthy controls(P<0.05).When investigating the other characteristic transcription factor of Treg,Helios,we found that Helios+ Tregs in CD4+T cells was also significantly decreased in senior pneumonia patients compared with controls(P<0.05).The m RNA level of Foxp3 in CD4+T cells was significantly lower in patients than in controls,whereas no differences were identified regarding the m RNA level of Helios.When stimulated with anti-CD3,anti-CD28,TGF-β,and IL-2,the m RNA levels of both Foxp3 and Helios in CD4+T cells were significantly lower in patients than in controls.Function analysis showed that the secretion of anti-inflammatory cytokines IL-10 and TGF-β was significantly decreased in CD4+T cells from patients.Also,the m RNA levels of IL-10 and TGF-β were significantly decreased in CD4+T cells from patients.Further function analysis revealed that the secretion of cytotoxic factors,granzyme B and perforin,was significantly lower in CD4+T cells from patients than those from controls.In addition,when the percentages of effector CD4+CD25-T cells and regulatory CD4+CD25+T cells were at 80: 20,50: 50,and 20: 80,the levels of thymidine incorporation were significantly higher in senior pneumonia patients than in healthy subjects.Also,the levels of thymidine incorporation were significantly higher in senior pneumonia patients when the percentages of effector CD8+T cells and regulatory CD4+CD25+T cells were at 80: 20 and 50: 50,suggesting that the immuno-suppressive function of Tregs in patients was decreased.When analyzing PSI and Treg parameters,we found that PSI in our cohort of senior pneumonia patients was inversely correlated with the frequency of Foxp3+ and Helios+ cells in CD4+T cells,and with the level of TGF-β secretion by CD4+T cells.No significant correlation between PSI and IL-10 secretion by CD4+T cells was found.Also,granzyme B or perforin secretion by Tregs was not correlated with PSI.Conclusions: The immune responses of Tregs in senior pneumonia patients are impaired,and are correlated with the severity of the disease.Improving the numbers and activation of Tregs may develop a novel immuno-therapy for senior pneumonia in the future.