抗原肽浓度对初始T细胞向Th1/Tc1、Th2/Tc2分化影响的研究

目的 研究不同浓度抗原肽(OVA)对初始CD4~+T细胞向Thl/Th2、初始CD8~+T细胞向Tc1/Tc2分化偏向性的影响.方法 采用系列浓度TCR特异性抗原肽与小鼠脾脏树突状细胞联合培养,然后刺激小鼠初始CD4~+或CD8~+T细胞.流式细胞术检测细胞内因子IFN-γ和IL-4的表达水平,同时用CFSE检测活化T细胞的增殖水平.结果 低浓度抗原肽刺激初始CD4~+T向Th2、初始CD8~+T向Tc2分化;而高浓度抗原肽刺激初始CD4~+T向Th1、初始CD8~+T向Tc1分化.Th细胞比Tc细胞受影响程度要明显.结论 抗原肽在很大浓度范围内均可以刺激初始T细胞的活化,但随着浓度的升高,分化方向从Th2、Tc2逐渐向Th1、Tc1倾斜.这一结论为动物实验中疫苗免疫剂量的控制提供了重要的参考价值.

Peptide concentration regulates priming of naive T cells to develop into Th1/Tc1 or Th2/Tc2 cells

Objective To study the effect of concentration of TCR-specific antigen peptides on priming naive CD4~+ T cells to develop into Th1/Th2 cells or naive CD8~+ T cells to develop into Tc1/Tc2 cells. Methods TCR-specific peptides with series of concentration were co-cultured with routine spleen DCs to activate murine naive CD4~+/CD8~+ T cells. The production of intracellular cytokines IFN-γand IL-4 were measured by flow cytometry. The dividing profile of activated T cells was analyzed by CFSE staining. Results Lower concentration of specific peptides favored Th2/Tc2 polarization while higher concentration benefited Th1/Tc1 polarization. The influence of peptides concentration on Th cells differentiation is higher than that on Tc cells. Conclusion Antigen peptides can stimulate activation of naive T cells in a wide range of concentration. However, with the increase of peptides concentration, activated T cells differentiated grad-ually from Th2/Tc2 to Th1/Tc1, which will provide significant value to control immunized dose of vaccine candidates in animal experiments.