Development and physiological role of gammadeltaT cells.

我们的研究结果表明：1)γ - δ - iel缺失与肠上皮细胞周转减少和MHCⅱ类分子表达下调有关。2)分析了由于beta_2M基因突变或TAP-1基因突变导致MHC I类分子表达缺失的小鼠以及beta_2M和TAP-1基因双合的小鼠CD8^+肠上皮内T淋巴细胞（IEL）的发育情况。在所有突变小鼠中，cd8α α ^+和cd8α α ^+ α - iel主要亚群的种群大小急剧减少。然而，在beta_2M*TCRdelta双突变小鼠中，CD8alphaalpha^+而非CD8alphabeta^+alpha - iel亚群显著扩增。因此，在缺乏γ δ - iel的情况下，β - 2m缺陷小鼠的α - iel数量超过野生型小鼠。这些结果表明，α β -和γ δ -IEL的cd8α α ^+淋巴细胞群的产生不依赖于β - 2m -和/或TAP-1依赖性的MHC I类分子，这些分子由IEL发生的解剖部位的控制细胞表达。3)皮内注射自身反应性T细胞后，δ ^<-/->小鼠的DTH反应和皮肤GVHD明显增强，持续时间比δ ^<+/->小鼠长。令人惊讶的是，在GVHD自发恢复后，delta^<-/->小鼠的表皮没有诱导对皮肤GVHD的抗性，而delta^<-/->小鼠的“易感”表皮含有大量的α β ^+ dEC，与delta^<+/->小鼠的“抗性”表皮相当。将δ ^<+/+>小鼠的第16天胎儿胸腺细胞注射到δ ^<-/->小鼠体内，在表皮中出现供体型γ δ ^+ dEC， γ δ ^+ dEC的重建使表皮对GVHD的保护性免疫反应恢复到接近正常水平。这些结果表明，γ - δ ^+ dEC对皮肤GVHD具有部位限制性保护作用。少

Our result shows :1) The absence of gammadelta-IEL is associated with a reduction in intestinal epithelial cell turnover and a downregulation of the expression of MHC class II molecules.2) The development of CD8^+ intestinal intraepitehlial T lymphocytes (IEL) was analyzed in mice that are deficient in the expression of MHC class I molecules owing to either a mutanted beta_2M gene or a mutanted TAP-1 gene and in mice doubly lomozygous for beta_2M and TAP-1 mutations. In all mutant mice, the population size of major CD8alphaalpha^+ and CD8alphabeta^+ alphabeta-IEL subsets was drastically reduced. In beta_2M*TCRdelta double mutant mice, however, the CD8alphaalpha^+ but not CD8alphabeta^+alphabeta-IEL subset expanded dramatically. Thus, in the absence of gammadelta-IEL,alphabeta-IEL in beta_2M deficient mice outnumbered those in wild-type littermates. These results indicate that the generation of CD8alphaalpha^+ lymphocyte population of alphabeta- and gammadelta-IEL is not dependent but t … More hat of CD8alphabeta^+ lymphocyte population of alphabeta-IEL is dependent on beta_2M- and/or TAP-1 dependent MHC class I molecules expressed by the controlling cells present in the anatomical site where the development of IEL takes place.3) After intradermal injection of the autoreactive T cells, delta^<-/-> mice developed significantly enhanced DTH responses and cutaneous GVHD,which persisted longer than those in delta^<+/-> mice. Surprisingly, resistance to the cutaneous GVHD was not induced in the epidermis of delta^<-/-> mice after spontaneous recovery from the GVHD,while the "susceptible" epidermis of delta^<-/-> mice contained large numbers of alphabeta^+ dEC comparable to those in the "resistant" epidermis of delta^<+/-> mice. Injection of day 16 fetal thymocytes from delta^<+/+> mice into delta^<-/-> mice resulted in the appearance of donor-type gammadelta^+ dEC in the epidermis and the reconstitution with the gammadelta^+ dEC restored the protective immune response of the epidermus against the GVHD to nearly normal levels. These results indicate that gammadelta^+ dEC are responsible for the site-restricted protection against cutaneous GVHD. Less