ABSTRACT
OBJECTIVE@#To assess the effect of neutralizing CD96 on natural killer (NK) cell functions in mice with pulmonary infection and explore the possible mechanism.@*METHODS@#Male BALB/c mice were randomly divided into infection group (Cm group), anti-CD96 treatment group (anti-CD96 group) and control group (=5). In the former two groups, was inoculated intranasal administration to establish mouse models of pulmonary infection, and the mice in the control group received intranasal administration of the inhalation buffer. In anti-CD96 group, the mice were injected with anti-CD96 antibody intraperitoneally at the dose of 250 μg every 3 days after the infection; the mice in Cm group received intraperitoneal injections of saline. The body weight of the mice was recorded daily. The mice were sacrificed 5 days after infection, and CD96 expression was detected by quantitative real-time PCR and Western blotting. HE staining and pathological scores were used to evaluate pneumonia of the mice. The inclusion body forming units (IFUs) were detected in the lung tissue homogenates to assess lung tissue chlamydia load. Flow cytometry and ELISA were used to assess the capacity of the lung NK cells to produce interferon-γ (IFN-γ) and regulate macrophages and Th1 cells.@*RESULTS@# infection inhibited CD96 expression in NK cells of the mice. Compared with those in Cm group, the mice in antiCD96 mice showed significantly milder lung inflammation ( < 0.05) and reduced chlamydia load in the lung tissue ( < 0.05). Neutralizing CD96 with anti-CD96 significantly enhanced IFN-γ secretion by the NK cells ( < 0.05) and augmented the immunoregulatory effect of the NK cells shown by enhanced responses of the lung macrophages ( < 0.05) and Th1 cells ( < 0.05).@*CONCLUSIONS@#Inhibition of CD96 alleviates pneumonia in -infected mice possibly by enhancing IFN-γ secretion by NK cells and augmenting the immunoregulatory effect of the NK cells on innate and adaptive immunity.
Subject(s)
Animals , Male , Mice , Antigens, CD , Chlamydia Infections , Chlamydia muridarum , Interferon-gamma , Killer Cells, Natural , Lung Injury , Mice, Inbred BALB C , Mice, Inbred C57BLABSTRACT
Objective:To observe the influence of the CD96 and CD71 expressions in the surface of leukemia stem cells (LSC) in the therapeutic effects and prognosis of the children with acute leukemia,and to clarify the relationships between the molecular biological characteristics of LSC in the children with leukemia and their therapeutic effects and prognosis.Methods:Eighty children with acute leukemia were selected as the subjects.Among them, 39 cases were acute lymphoblastic leukemia (ALL) and 41 cases were acute myeloid leukemia (AML).The CD96 and CD71 expressions on the surface of LSC were detected with flow cytometry;the therapeutic effects of the first cycle chemotherapy, the survival rate of 5-year, the incidence of infection after chemotherapy, the recurrence rate after chemotherapy, and the incidence of extramedullary infiltration of the children were observed and compared.Results: The CD96 expression on the surface of LSC was positive in 38 cases (47.5%) and the CD71 expression on the surface of LSC was positive in 45 cases (56.3%);the difference of positive expression rates of CD96 and CD71 was not significant (χ2=1.227, P=0.268).The positive expression rates of CD96 and CD71 on the surface of LSC of the children with AML were significantly higher than those in the children with ALL, and the differences were statistically significant (χ2=22.225, χ2=34.028, P<0.01).The distribution of therapeutic effects and the clinical efficiency of the first cycle chemotherap, in the children with negative CD96 expression on the surface of LSC were superior to those with positive CD96 expression on the surface of LSC;the distribution of therapeutic effects and the clinical efficiency of the first cycle chemotherapy in the children with negative CD71 expression on the surface of LSC were superior than those with positive CD71 expression on the surface of LSC;the differences between two groups were statistically significant (χ2=11.323, χ2=16.589, P<0.05;U=2.939, U=2.291, P<0.05).The survival rate of 5-year in the children with negative CD96 expression on the surface of LSC was higher than those with positive CD96 expression;the incidence of infection after chemotherapy,the recurrence rate after chemotherapy and the incidence of extramedullary infiltration were lower than those with positive CD96 expression.The incidence of infection after chemotherapy and the recurrence rate after chemotherapy in the children with negative CD71 expression on the surface of LSC were lower than those with positive CD71 expression,and the differences between two groups were statistically significant (χ2=5.051,χ2=13.288, P<0.05).Conclusion: The expressions of CD96 and CD71 on the surface of LSC in the children with acute leukemia has relationship with the subtypes of the disease and the therapeutic effects of the first cycle chemotherapy, which can be used as markers for the diagnosis and evaluation of therapeutic effects.The expression level of CD96 is related to the prognosis of the patients, which can be used as an indicator for predicting the prognosis of patients.