Effect Of CD40 On Cytotoxic Offector Function In CD8+T Cell Of Mice With Cigarette Smoke-Induced Emphysema

Objective To explore the effect of CD40 on cytotoxic effector function of CD8+ T cell of the mice with cigarette smoke-induced emphysema.Methods Total 40 male C57 mice were divided into four groups including CD40+/+ control group, CD40+/+ smoke-exposure group, CD40-/-control group, CD40-/-smoke-exposure group. The smoke-exposure groups were exposed to cigarette smoke for 24 weeks to establish emphysema model. Morphological changes were evaluated by linear intercepts. The percentage of perforin, granzyme B positive cells were evaluated by immunohistochemistry. The mRNA expression of perforin, granzyme B, IL-27 were measured by fluorescent real time quantitative polymerase chain reaction (RT-PCR).The IL-27 cytokine level was tested by enzyme-linked immunosorbent assay (ELISA).Results(1)The mean linear intercepts in CD40+/+ smoke.exposure group was significantly higher than CD4+/+ control group and CD40-/-control group (all P<0.05).The mean linear intercepts of CD40-/-smoke-exposure group decresed compared with CD40+/+ smoke.exposure(P<0.05).The mean linear intercepts of CD40-/-smoke.exposure group was higher than CD40+/+ control group,CD40-/- control group(all P<0.05).(2)The percentage of perforin positive and granzyme B positive cells in CD40++/+ smoke-exposure group were significantly higher than CD40+/+ control group and CD40-/-control group(all P<0.05).The percentage of perforin positive and granzyme B positive cells in CD40-/-smoke-exposure group were lower than those in CD40+/+ smoke-exposure group(P<0.05).(3)RT-PCR results showed that the mRNA expression of perforin,granzyme B and IL-27 in CD40+/+ smoke-exposure group were significantly higher than CD40++/+ control group and GD40-control group(LL P<0.05).The mRNA exppression of perforin,granzyme B and IL-27 in CD40-/- smoke.exposure group decresed than CD40+/+ smoke-exposure group(P<0.05).(4)ELISA results showed that the level of IL-27 in CD40+/+ smoke.exposure group was significantly higher than CD40+/+ control group and CD40-/-control group(all P<0.05).The level of IL-27 in CD40-/-smoke-exposure group decresed than CD40+/+ smoke.exposure group.Conclusion Block the CD40-CD40L passway could inhibit the cytotoxic effector function of CD8 T cells in the lungs of mice with cigarette smoke-induced emphysema and alleviate the degree of emphysema.