Hongbin Jiang1, Huili Gong2, Qing Zhang3, Jin Gu3, Li Liang3, Jun Zhang4. 1. Department of Emergency, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China. 2. Tuberculosis Section, Shanghai Pudong New Area Pulmonary Hospital, Shanghai 201209, China. 3. Clinic and Research Center of Tuberculosis, Shanghai Key Lab of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China. 4. Department of Laboratory Medicine, Shanghai DeltaHealth Hospital, Shanghai 201702, China.
Abstract
BACKGROUND: Cytolytic activity against mycobacteria tuberculosis (MTB) within the infected macrophage is a crucial step in the immunity against TB infection, as MTB is an intracellular bacterium. Cytotoxic molecules such as perforin and granzymes produced by cytolytic T cells directly participate in this process. In this study, we evaluated the cytotoxicity function employing flow cytometry analysis of the level of expression of interferon-γ (IFN-γ), perforin and granzyme B in CD8+ T cells from patients with active pulmonary TB (PTB), stable PTB and healthy controls, and explored whether MTB antigen (MTB Ag)-stimulated cytotoxic molecules would be useful for monitoring responses to anti-TB treatment. METHODS: Intracellular IFN-γ, perforin, and granzyme B were measured by flow cytometry in CD8+ T lymphocyte populations from peripheral blood mononuclear cells before and after stimulation with ESAT-6 and CFP-10 peptides for 72 hours. A total of 38 healthy controls, 52 PTB patients after treatment for 2 months and 58 patients with active PTB were enrolled. RESULTS: The positive rate of IFN-γ+ CD8+ T cells was expressed higher in active PTB patients and stable PTB compared to healthy controls. Expression of perforin in CD8+ T lymphocytes was lower in the active PTB than the stable PTB. Positive downregulation of perforin and granzyme B after stimulation with ESAT-6 and CFP-10 peptides in active PTB and stable PTB was seen. IFN-γ was upregulated after stimulation. ROC curve analysis showed that the area under the curve (AUC) of perforin and perforin + IFN-γ after stimulation were 0.766 (P=0.000), 0.802 (P=0.000), respectively. CONCLUSIONS: Our results show that expression of perforin in CD8+ T lymphocytes is downregulated in PTB infection and ESAT-6 and CFP-10 peptides might participate in the downregulation process. This finding cautiously suggests that MTB Ag-stimulated perforin downregulation and IFN-γ upregulation might be a potential index for monitoring therapy response in active PTB patients.
BACKGROUND: Cytolytic activity against mycobacteria tuberculosis (MTB) within the infected macrophage is a crucial step in the immunity against TB infection, as MTB is an intracellular bacterium. Cytotoxic molecules such as perforin and granzymes produced by cytolytic T cells directly participate in this process. In this study, we evaluated the cytotoxicity function employing flow cytometry analysis of the level of expression of interferon-γ (IFN-γ), perforin and granzyme B in CD8+ T cells from patients with active pulmonary TB (PTB), stable PTB and healthy controls, and explored whether MTB antigen (MTB Ag)-stimulated cytotoxic molecules would be useful for monitoring responses to anti-TB treatment. METHODS: Intracellular IFN-γ, perforin, and granzyme B were measured by flow cytometry in CD8+ T lymphocyte populations from peripheral blood mononuclear cells before and after stimulation with ESAT-6 and CFP-10 peptides for 72 hours. A total of 38 healthy controls, 52 PTB patients after treatment for 2 months and 58 patients with active PTB were enrolled. RESULTS: The positive rate of IFN-γ+ CD8+ T cells was expressed higher in active PTB patients and stable PTB compared to healthy controls. Expression of perforin in CD8+ T lymphocytes was lower in the active PTB than the stable PTB. Positive downregulation of perforin and granzyme B after stimulation with ESAT-6 and CFP-10 peptides in active PTB and stable PTB was seen. IFN-γ was upregulated after stimulation. ROC curve analysis showed that the area under the curve (AUC) of perforin and perforin + IFN-γ after stimulation were 0.766 (P=0.000), 0.802 (P=0.000), respectively. CONCLUSIONS: Our results show that expression of perforin in CD8+ T lymphocytes is downregulated in PTB infection and ESAT-6 and CFP-10 peptides might participate in the downregulation process. This finding cautiously suggests that MTB Ag-stimulated perforin downregulation and IFN-γ upregulation might be a potential index for monitoring therapy response in active PTB patients.
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