Katakai T, Mori K J, Masuda T, Shimizu A
Center for Molecular Biology and Genetics, Kyoto University, Japan.
Int Immunol. 1998 Sep;10(9):1325-34. doi: 10.1093/intimm/10.9.1325.
The vast majority of CD4+ T cells infiltrating into gastric mucosa (GM) and in the draining (gastric) lymph node (GLN) shows an activated/memory phenotype, CD45RB(low) L-selectin(low) CD44(high), in neonataly thymectomized BALB/c mice bearing autoimmune gastritis (AIG), indicating that these cells are actively involved in this disease. CD4+ T cells sort-purified from GLN expressed mRNAs encoding for both IFN-gamma and IL-4. However, those infiltrating into GM expressed very low levels of IL-4 mRNA, even though they strongly expressed IFN-gamma mRNA. Among CD4+ T cells separated from AIG mice expressing detectable levels of either IFN-gamma or IL-4 by intracellular staining, less than one-seventh expressed IL-4 and thus most of them expressed IFN-gamma in GM, whereas roughly half and one-third expressed IL-4 in GLN and spleen respectively. These findings indicate that the Th1 cells predominantly infiltrate into autoimmune lesions and Th2 cells are mainly resident in the regional LN. We further set up an in vitro model system of transendothelial migration using a murine endothelial cell line, F-2, and found that Th1 cells in CD4+ T cells separated from lymphoid tissues of AIG mice preferentially passed through the monolayer of endothelial cells while only a small portion of Th2 cells did so. This differing ability of transendothelial migration and localization might explain the dominance of Th1 cells destroying the tissue in focal lesions without inhibition by the Th2 cells, in spite of both subsets being simultaneously activated in AIG mice, and the functions of each T cell subset seems to be mutually exclusive.
在患有自身免疫性胃炎（AIG）的新生胸腺切除BALB/c小鼠中，浸润到胃黏膜（GM）和引流（胃）淋巴结（GLN）中的绝大多数CD4 + T细胞表现出活化/记忆表型，即CD45RB（低）L-选择素（低）CD44（高），这表明这些细胞积极参与了该疾病。从GLN中分选纯化的CD4 + T细胞表达编码IFN-γ和IL-4的mRNA。然而，浸润到GM中的细胞IL-4 mRNA表达水平非常低，尽管它们强烈表达IFN-γ mRNA。在通过细胞内染色表达可检测水平的IFN-γ或IL-4的AIG小鼠分离出的CD4 + T细胞中，不到七分之一表达IL-4，因此它们中的大多数在GM中表达IFN-γ，而在GLN和脾脏中分别约有一半和三分之一表达IL-4。这些发现表明，Th1细胞主要浸润到自身免疫病变中，而Th2细胞主要驻留在局部淋巴结中。我们进一步使用小鼠内皮细胞系F-2建立了一个跨内皮迁移的体外模型系统，发现从AIG小鼠淋巴组织分离的CD4 + T细胞中的Th1细胞优先穿过内皮细胞单层，而只有一小部分Th2细胞能做到。这种跨内皮迁移和定位能力的差异可能解释了尽管在AIG小鼠中两个亚群同时被激活，但Th1细胞在局灶性病变中破坏组织时不受Th2细胞抑制的主导地位，并且每个T细胞亚群的功能似乎是相互排斥的。
