T‐bet modulates the antibody response and immune protection during murine malaria

CD4⁺ T‐cell subtypes govern the synthesis of different Ab isotypes and other immune functions. The influence of CD4⁺ T‐cell differentiation programs on isotype switching and other aspects of host immunological networks during malaria infection are currently poorly understood. Here, we used Tbx21^?/? mice deficient for T‐bet, a regulator of Th1 CD4⁺ T‐cell differentiation, to examine the effect of Th1 CD4⁺ T cells on the immune protection to nonlethal murine malaria Plasmodium yoelii 17XNL. We found that Tbx21^?/? mice exhibited significantly lower parasite burden that correlated with elevated levels of IgG1, indicating that T‐bet‐dependent Ab isotype switching may be responsible for lower parasite burden. Absence of T‐bet was also associated with a transient but significant loss of T cells during the infection, suggesting that T‐bet may suppress malaria‐induced apoptosis or induce proliferation of T cells. However, Tbx21^?/? mice produced greater numbers of Foxp3⁺CD25⁺ regulatory CD4⁺ T cells, which may contribute to the early contraction of T cells. Lastly, Tbx21^?/? mice exhibited unimpaired production of IFN‐γ by a diverse repertoire of immune cell subsets and a selective expansion of IFN‐γ‐producing T cells. These observations may have implications in malaria vaccine design.     

Prognostic impact of tumour-infiltrating Th2 and regulatory T cells in classical Hodgkin lymphoma

Classical Hodgkin Lymphoma (cHL) is morphologically characterized by a small number of tumour cells, Hodgkin and Reed-Sternberg (HRS) cells, surrounded by numerous tumour-infiltrating lymphocytes (TIL). The functional role of these TIL is still controversial. While generally considered to represent an anti-tumour immune response, TIL in cHL might result from the profoundly deregulated immunity of cHL patients. Eighty-seven cases of cHL were available to evaluate the prognostical significance of tumour-infiltrating cytotoxic T lymphocytes (CTL), T helper 1 (Th1) cells, T helper 2 (Th2) cells and regulatory T cells (Treg). We confirm that in cHL the microenvironment is dominated by Th2 cells and Treg and show that large numbers of Th2 cells are associated with significantly improved disease-free survival (p = 0.021) and event-free survival (p = 0.012). Furthermore, a high ratio of Treg over Th2 cells resulted in a significantly shortened disease-free survival (p = 0.025). These observations suggest that Treg may exert inhibitory effects on anti-tumour immune responses mediated through Th2 cells and that Th2 cells may be more important for effective anti-tumour immunity than anticipated.     

祛风止痉方对哮喘大鼠转录因子T-bet GATA-3及TNF-α的调节作用

[目的]证实祛风止痉方对哮喘大鼠治疗作用的部分机理是通过对转录因子T-bet、GATA-3及TNF-α的调节起作用的。[方法]60只大鼠随机分组为哮喘模型组、正常对照组及给药组(高中低剂量)建立大鼠哮喘模型,并分别给药。用RT-PCR检测T-bet、GATA-3表达水平,双抗体夹心ELISA法测定TNF-α浓度。[结果]模型组大鼠外周血中转录因子GATA-3高于正常对照组及给药组,比较有统计学意义(P<0.05);低剂量组表达高于高剂量组,比较有统计学意义(P<0.05);高剂量组与正常组比较无统计学意义(P>0.05);中低剂量组比较无统计学意义(P>0.05);中低两组高于正常组,比较有统计学意义(P<0.05);中剂量组与高剂量组比较无统计学意义(P>0.05)。模型组大鼠外周血中转录因子T-bet的表达量低于正常对照组及给药组,其差异具有统计学意义(P<0.05);低剂量组低于高剂量组,比较有统计学意义(P<0.05);中高剂量高于模型组,比较有统计学意义(P<0.05)。血清中TNF-α的表达,模型组高于正常组,比较有统计学意义(P<0.05);高量组低于模型组,比较有统计学意义(P<0.05)。[结论]祛风止痉方可抑制哮喘大鼠外周血中转录因子GATA-3的表达,增加转录因子T-bet的表达,以恢复Th1/Th2平衡,同时可减低TNF-α浓度,从而降低哮喘大鼠气道高反应性,达到治疗支气管哮喘的目的。