Ananlysis Of Expression And Characteristics Of Co-inhibitory Molecules BTLA/HVEM On CD4~+CD25~+Foxp3~+Regulatory T Cells From Pulmonary Tuberculosis Patients

[AIM] To elucidate the expression and characteristics of co-inhibitory molecules BTLA and HVEM on CD4+CD25+Foxp3+regulatory T cells (Treg) from pulmonary tuberculosis patients through analyzing the ratio of Treg/CD4+T and its relationship with the clinic baseline characteristics and investigating the expression of BTLA and HVEM on Treg and the correlations to Treg/CD4+T ratio, the functional molecular of Treg PD-L1.[METHODS] The methods of multi-color fluorescence labeling and Flow Cytometry were used to detect CD4+CD25+Foxp3+regulatory cells and the expression of BTLA, HVEM, PD-L1or PD-1on CD4+CD25+Foxp3+regulatory cells. The antibodies against the antigens of Mycobacterium tuberculosis (MTB) LAM, protein16KDa and38KDa were determined by protein chip technology. The progressing of pulmonary tuberculosis was evaluated by the diagnosed results gained from computer tomography imaging. The drug-resistance of Mycobacterium tuberculosis’was evaluated with Russell medium.[RESULTS] Compared with healthy control, the ratio of CD4+CD25+Foxp3+Treg/CD4+T evidently increased. Moreover, this ratio in patients with anti-MTB antibody presenting positive or pulmonary progressing seriously was obviously higher, compare with those with anti-MTB antibody presenting negative or pulmonary progressing mildly. The co-inhibitory molecules BTLA and its ligand HVEM were markedly down-regulated on CD4+CD25+Foxp3+regulatory cells of tuberculosis patients and presented positively correlations to Treg/CD4+T ratio, PD-L1and PD-1expression on Treg.[CONCLUSION] The over-proliferation of CD4+CD25+Foxp3+regulatory cells contributes to the inhibition of effective immune response against MTB and the progressing of pulmonary tuberculosis. The down-regulation of co-inhibitory signals BTLA/HVEM enables the over-proliferation of Treg in patients with pulmonary tuberculosis.