Aicher W K, Fujihashi K, Taguchi T, McGhee J R, Yamamoto M, Eldridge J H, Gay S, Kiyono H
Department of Microbiology, University of Alabama, Birmingham 35294.
Eur J Immunol. 1992 Jan;22(1):137-45. doi: 10.1002/eji.1830220121.
The mucosal immune system of the gastrointestinal (GI) tract consists of Peyer's patches (PP), which are IgA inductive sites, and more diffuse effector regions which include cells in the intraepithelial lymphocyte (IEL) compartment. Since autoimmune MRL lpr/lpr (MRL/lpr) mice develop a proliferating CD3+, CD4-, CD8- (double negative; DN), B220+ T cell subset in systemic lymphoid tissue, we have initiated studies to determine the distribution of CD3+, DN, B220+ T cells (B220+ T cells or lpr/lpr T cells) in the GI immune system. Specifically, we examined T cell subsets separated according to expression of CD4, CD8, Thy-1, B220, alpha/beta T cell receptor (TcR) and gamma/delta TcR in PP and IEL of MRL/lpr mice at 6, 12 and 21 weeks of age. Increased numbers of CD3+ T cells were noted in both PP and spleen of 12- and 21-week-old mice in which the development of autoimmune disorders were also evident. However, normal numbers of CD3+ IEL T cells were seen in MRL/lpr mice in all three age groups tested. When the presence of T cell lymphadenopathy was examined in both IgA inductive and effector tissues, the PP followed the B220+ T cell pattern seen in the spleen, where approximately 30%-50% of CD3+ T cells in the PP of 12- and 21-week-old MRL/lpr mice expressed the phenotype of lpr/lpr T cells and greater than 90% were alpha/beta TcR+. On the other hand, B220+ T cells had not developed in PP or spleen of 6-week-old MRL/lpr mice. Of interest was the finding that IEL from lpr/lpr homozygous mice did not contain B220+ T cells in any age group tested. In this regard, the IEL of MRL/lpr mice comprised an identical pattern and frequency of CD4-/CD8+, CD4+/CD8-, DN and CD4+/CD8+ (double positive, DP) T cell subsets as their normal counterparts (i.e. MRL +/+, BALB/c and C3H/HeN mice) which consisted of approximately 75%, approximately 7.5%, approximately 7.5% and approximately 10%, respectively. Further, Thy-1, gamma/delta TcR and alpha/beta TcR expression in these four subsets of MRL/lpr IEL were very similar to normal mice. These results suggest that the intestinal IEL compartment is minimally affected by the lpr/lpr mutation which induces T cell abnormalities and indicate that B220+ T cells do not preferentially home to IEL. Further, our results support the concept that IEL T cells develop as a separate T cell lineage from thymus-derived cells.
胃肠道（GI）的黏膜免疫系统由派尔集合淋巴结（PP）组成，PP是IgA诱导部位，还有更弥散的效应区域，包括上皮内淋巴细胞（IEL）区室中的细胞。由于自身免疫性MRL lpr/lpr（MRL/lpr）小鼠在全身淋巴组织中会出现增殖的CD3⁺、CD4⁻、CD8⁻（双阴性；DN）、B220⁺T细胞亚群，我们已开展研究以确定CD3⁺、DN、B220⁺T细胞（B220⁺T细胞或lpr/lpr T细胞）在胃肠道免疫系统中的分布。具体而言，我们检测了6周、12周和21周龄MRL/lpr小鼠的PP和IEL中根据CD4、CD8、Thy-1、B220、α/βT细胞受体（TcR）和γ/δTcR表达分离的T细胞亚群。在12周龄和21周龄小鼠的PP和脾脏中均发现CD3⁺T细胞数量增加，此时自身免疫性疾病的发展也很明显。然而，在所有测试的三个年龄组中，MRL/lpr小鼠的CD3⁺IEL T细胞数量正常。当在IgA诱导组织和效应组织中检查T细胞淋巴结病的存在时，PP呈现出与脾脏中B220⁺T细胞模式相同的情况，在12周龄和21周龄MRL/lpr小鼠的PP中，约30% - 50%的CD3⁺T细胞表达lpr/lpr T细胞的表型，且超过90%为α/βTcR⁺。另一方面，6周龄MRL/lpr小鼠的PP或脾脏中尚未出现B220⁺T细胞。有趣的是，在任何测试年龄组中，lpr/lpr纯合小鼠的IEL中均未发现B220⁺T细胞。在这方面，MRL/lpr小鼠的IEL中CD4⁻/CD8⁺、CD4⁺/CD8⁻、DN和CD4⁺/CD8⁺（双阳性，DP）T细胞亚群的模式和频率与它们的正常对照（即MRL +/+、BALB/c和C3H/HeN小鼠）相同，分别约为75%、约7.5%、约7.5%和约10%。此外，MRL/lpr IEL的这四个亚群中Thy-1、γ/δTcR和α/βTcR的表达与正常小鼠非常相似。这些结果表明，肠道IEL区室受诱导T细胞异常的lpr/lpr突变影响最小，表明B220⁺T细胞不会优先归巢到IEL。此外，我们的结果支持IEL T细胞作为与胸腺来源细胞不同的T细胞谱系发育而来的概念。
