Jöhrens K, Anagnostopoulos I, Dürkop H, Stein H
Institute for Pathology, Charité, Campus Benjamin Franklin, Medical University Berlin, Germany.
Histopathology. 2006 Mar;48(4):343-52. doi: 10.1111/j.1365-2559.2005.02305.x.
To investigate T-bet expression profiles in various lymphoid tissue diseases caused by intracellular pathogens and to compare them in disorders without an infective aetiology. Murine and in vitro experiments have shown that the expression/induction of T-bet, the master regulator of Th1 differentiation, can be achieved by obligate intracellular pathogens and high interferon (IFN)-gamma levels.
Lymph node biopsies were analysed immunohistochemically employing single and double labelling for T-bet and CD20, CD4, CD8 and CD30 detection.
In disorders associated with high IFN-gamma levels and intracellular pathogens (infectious mononucleosis, HIV-associated lymphadenopathy, cat-scratch disease, and toxoplasmic lymphadenitis), T-bet-expressing CD4 cells were accompanied by significant numbers of T-bet-positive CD8 and B cells. A similar profile was also found in histiocytic necrotizing (Kikuchi) lymphadenitis, a disease of unknown cause. In contrast, T-bet expression in disorders without an infective aetiology was observed in only a small portion of lymphocytes.
Increased T-bet expression does not only identify intracellular infections in lymphoid tissue associated with high IFN-gamma levels, but also implies that, under these conditions, it becomes induced in B cells, which apparently support the Th1 response. T-bet expression in Kikuchi lymphadenitis underscores the hypothesis that it is caused by an intracellular microorganism.
研究T-bet在由细胞内病原体引起的各种淋巴组织疾病中的表达谱,并将其与无感染病因的疾病进行比较。小鼠和体外实验表明,Th1分化的主要调节因子T-bet的表达/诱导可由专性细胞内病原体和高干扰素(IFN)-γ水平实现。
采用免疫组织化学方法对淋巴结活检组织进行分析,使用单标和双标检测T-bet以及CD20、CD4、CD8和CD30。
在与高IFN-γ水平和细胞内病原体相关的疾病(传染性单核细胞增多症、HIV相关淋巴结病、猫抓病和弓形虫淋巴结炎)中,表达T-bet的CD4细胞伴有大量T-bet阳性的CD8细胞和B细胞。在病因不明的组织细胞坏死性(菊池)淋巴结炎中也发现了类似的情况。相比之下,在无感染病因的疾病中,仅在一小部分淋巴细胞中观察到T-bet表达。
T-bet表达增加不仅可识别与高IFN-γ水平相关的淋巴组织中的细胞内感染,还意味着在这些条件下,B细胞中也会诱导T-bet表达,这显然支持Th1反应。菊池淋巴结炎中T-bet的表达强调了其由细胞内微生物引起的假说。