The Clinical Significance Of Follicular Helper T Cells And PD-1,IL-21in Pulmonary Tuberculosis

Objective: Follicular helper T lymphocyte(Tfh)is an independent subset of CD4+T cells that are truly responsible for helper B cells.It is involved in the formation of germinal center GC,which promotes the differentiation of high-affinity B cells into plasma cells or memory cells.It can also assist B lymphocytes to produce antibodies and help antibody class switching,which is closely related to the development of various autoimmune diseases,immunodeficiency diseases and infectious diseases.Tfh cells continue to express CXCR5,ICOS and PD-1.CXCR5 is an important "transporter molecule" for Tfh migration and localization.ICOS binds to and interacts with its receptor ICOSL to promote Tfh cell production.PD-1 is a negative regulatory receptor on the surface of T and B lymphocytes,inhibits the proliferation of Tfh cells,and plays an important role in regulating infectious immunity caused by microorganisms.IL-21 is a major cytokine that performs effector function in Tfh cells and is involved in many aspects of the regulation of the body's immune system.This study intends to use Tfh cells,PD-1 and IL-21 as research targets,and observe their expression patterns and trends in different stages of PTB,and explore the expression of Tfh cells,PD-1 and IL-21 in PTB.It can not only reveal the immunological role and clinical significance of Tfh cells in tuberculosis,but also provide a theoretical basis for exploring the diagnosis and treatment evaluation of tuberculosis diseases.Methods: In this study,all PTB patients came from the Tuberculosis Department of Haihe Hospital of Tianjin.Forty newly diagnosed smear-positive tuberculosis patients(PTB group)and 40 healthy controls(HC group)were diagnosed as having normal chest radiographs and various indicators.The PTB group was divided into two groups involving PTB-X3 and PTB-X2 according to the range of lung field involved.According to the results of sputum smear after the treatment cycle,PTB patients were divided into PTB-SN and PTB-SP.According to the results of imaging examination,TB patients were divided into PTB-os and PTB-s.Blood samples were collected at the end of two months,five months and six months in the tuberculosis group.Three tests were carried out:1.Tfh cells(CD4+CXCR5+Tfh/Lym cell ?CD4+CXCR5+ICOS+Tfh/CD4+CXCR5+Tfh)were detected by flow cytometry with anti-CD4,anti-CXCR5,anti-ICOS.2.Flow cytometry was used to detect PD-1(CD4+CXCR5+PD-1+Tfh/CD4+CXCR5+Tfh).3.ELISA was used to detect the level of IL-21 in serum.The expression and mechanism of Tfh cells,PD-1 and IL-21 in PTB were analyzed by comprehensive comparison.Results: The levels of CD4+CXCR5+Tfh and CD4+CXCR5+ICOS+Tfh in PTB were significantly higher than those of HC.CD4+CXCR5+Tfh in PTB-X2 were significantly lower than PTB-X3,and the difference was statistically significant.There was no significant difference between the two groups in CD4+CXCR5+ICOS+Tfh cells.The PD-1 in PTB was significantly higher than that of HC.The PD-1 in PTB-X2 was significantly lower than that in PTB-X3,the difference was statistically significant.The level of IL-21 in PTB was significantly higher than HC,and the difference was statistically significant.There was no significant difference in IL-21 between the PTB-X2 and PTB-X3.The CD4+CXCR5+Tfh in the PTB-SN and the PTB-SP showed a downward trend during the treatment cycle,and there was a statistical difference between the groups.There was no statistical difference between the two groups in PD-1 and IL-21.The CD4+CXCR5+Tfh in PTB-os and PTB-s showed a downward trend during the treatment cycle,and there was no statistical difference between the groups.The PD-1of the two groups decreased slowly,and there was no statistical difference between the two groups.There was no statistical difference between the two groups in IL-21.Conclusions: The CD4+CXCR5+Tfh,CD4+CXCR5+ICOS+Tfh,PD-1 and IL-21 play an immunological role in the pathogenesis of PTB.CD4+CXCR5+Tfh and PD-1can be used as indicators to reflect the severity of the disease;CD4+CXCR5+Tfh can be used as an indicator to reflect the outcome of sputum smear.IL-21 cannot be used as an indicator of disease severity and sputum smear outcome.Therefore,monitoring the changes of Tfh cells and PD-1 in PTB can help to understand the stage of tuberculosis development and can indicate the efficacy and outcome of treatment of tuberculosis patients.