Kühl Anja A, Pawlowski Nina N, Grollich Katja, Loddenkemper Christoph, Zeitz Martin, Hoffmann Jörg C
Medizinische Klinik I, and Institute of Pathology, Charité, University Medicine Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, Berlin D-12200, Germany.
J Leukoc Biol. 2007 Jan;81(1):168-75. doi: 10.1189/jlb.1105696. Epub 2006 Oct 13.
The role of gammadelta T cells in inflammatory bowel disease (IBD) is still controversial. Although gammadelta T cells induce IBD in immunodeficient animals, others suggest a protective role of gammadelta T cells. Therefore, this study was conducted in order to elucidate the effect of gammadelta T cell depletion/deficiency on different IBD animal models. Mice depleted of or deficient in gammadelta T cells were exposed to dextran sodium sulfate (DSS) in order to induce colitis. In addition, gammadelta T cells were depleted in mice with terminal ileitis (TNFDeltaARE) or colitis due to interleukin 2 deficiency (IL-2 ko). Finally, DSS-induced colitis was studied in mice deficient in interferon gamma (IFN-gamma ko) upon gammadelta T cell depletion. Depletion of gammadelta T cells aggravated DSS-induced colitis and terminal ileitis of TNFDeltaARE mice. Exacerbated DSS-induced colitis was also found in gammadelta T cell-deficient mice. IL-2 ko mice showed increased mortality upon early (starting at 4 wk of age) but not late depletion (starting at 8 wk of age). Early gammadelta T cell depletion or deficiency resulted in increased IFN-gamma production by both lamina propria lymphocytes and splenocytes in every model investigated herein. In IFN-gamma ko mice, gammadelta T cell depletion did not affect the development and course of DSS-induced colitis. The protective effect of gammadelta T cells in IBD was confirmed in various IBD animal models. Particularly, during the early phase of intestinal inflammation, gammadelta T cells appear to be important. The mechanism seems to involve the control of IFN-gamma production and epithelial regeneration.
γδ T细胞在炎症性肠病（IBD）中的作用仍存在争议。尽管γδ T细胞在免疫缺陷动物中可诱发IBD，但也有研究表明γδ T细胞具有保护作用。因此，本研究旨在阐明γδ T细胞耗竭/缺陷对不同IBD动物模型的影响。将γδ T细胞耗竭或缺陷的小鼠暴露于葡聚糖硫酸钠（DSS）以诱导结肠炎。此外，在患有终末回肠炎（TNFDeltaARE）或因白细胞介素2缺乏（IL-2基因敲除小鼠）导致结肠炎的小鼠中耗竭γδ T细胞。最后，研究了γδ T细胞耗竭后干扰素γ缺陷（IFN-γ基因敲除小鼠）小鼠的DSS诱导结肠炎情况。γδ T细胞的耗竭加重了DSS诱导的结肠炎以及TNFDeltaARE小鼠的终末回肠炎。在γδ T细胞缺陷小鼠中也发现DSS诱导的结肠炎加剧。IL-2基因敲除小鼠在早期（4周龄开始）而非晚期（8周龄开始）耗竭γδ T细胞后死亡率增加。在本文研究的每个模型中，早期γδ T细胞耗竭或缺陷均导致固有层淋巴细胞和脾细胞产生的IFN-γ增加。在IFN-γ基因敲除小鼠中，γδ T细胞耗竭不影响DSS诱导结肠炎的发生和进程。在各种IBD动物模型中均证实了γδ T细胞在IBD中的保护作用。特别是在肠道炎症的早期阶段，γδ T细胞似乎很重要。其机制似乎涉及对IFN-γ产生和上皮再生的控制。
