4-1BB在人外周血γδT细胞活化中的协同刺激作用

采用结核杆菌(Mtb)低分子多肽刺激人外周血单个核细胞,流式细胞术(FCM)检测不同活化时相γδT细胞膜表面4-1BB分子的表达;用阻断型4-1BB配体(4-1BBL)单抗阻断4-1BB/4-1BBL信号,FCM检测γδT细胞的增殖比率和细胞内产生IFN-γ的情况,同时与阻断CD28/B7-1信号相比较。结果显示,静止的γδT细胞膜表面不表达4-1BB分子,Mtb抗原刺激后6 h,4-1BB即有明显表达(29.71%),48 h达到高峰(49.79%);与未阻断组相比,阻断4-1BB/4-1BBL信号,γδT细胞的增殖效应和细胞内IFN-γ的产生均明显下降(P<0.01),与CD28/B7-1信号阻断组相比,差异无显著性(P>0.05)。提示4-1BB/4-1BBL信号同CD28/B7-1信号一样,可为γδT细胞活化提供协同刺激作用。

Costimulatory role of 4-1BB in the activation of human peripheral blood γδT cells

Peripheral blood mononuclear cells(PBMC) were stimulated in vitro by a low-molecular peptide antigen of Mycobacterium tuberculosis(Mtb-Ag) expression of 4-1BB molecule on γδT cells was measured by flow cytometry(FCM) at different times after stimulation.By using the anti-4-1BB ligand(4-1BBL) monoclonal antibody to block the co-stimulatory signal of 4-1BB/4-1BBL interaction,the proliferative rate and the intracellular production of IFN-γ of γδT cells were detected by FCM.The experimental results showed that the 4-1BB molecule was expressed only on the activated γδT cells,and the surface expression of this molecule reached its peak at 48 hours after stimulation with Mtb-Ag.Meanwhile,the proliferative rate and the intracellular IFN-γ of γδT cells are obviously decreased after blockage of the costimulatory signal induced by 4-1BB/4-1BBL interaction.These results suggest that the costimulatory signal induced by the 4-1BB/4-1BBL interaction may play an important role in the activation and proliferation of γδT cells.