Farstad I N, Halstensen T S, Lien B, Kilshaw P J, Lazarovits A I, Brandtzaeg P
Laboratory for Immunohistochemistry and Immunopathology (LIIPAT), University of Oslo, National Hospital, Norway.
Immunology. 1996 Oct;89(2):227-37. doi: 10.1046/j.1365-2567.1996.d01-727.x.
Two alternative integrins involved in mucosal homing (alpha 4 beta 7) or epithelial retention (alpha E beta 7) of lymphocytes were examined in the human gut. The distribution of the beta 7 subunit [monoclonal antibody (mAb) M301] was bimodal in that it was strongly expressed by alpha E beta 7 + cells but weakly by alpha 4 beta 7 + cells. More than 90% of intraepithelial lymphocytes (IEL), including the minor subsets of CD4+, T-cell receptor (TCR) gamma/delta +, and CD3- cells, expressed alpha E beta 7 as did most lamina propria CD8+ (88%) and a fraction (36%) of CD4+ lymphocytes. Conversely, B-lineage cells (CD19+) and macrophages (CD68+) were negative. In gut-associated lymphoid tissue (GALT: Peyer's patches and appendix) only a few (< 5%) cells were positive for alpha E beta 7 (confined to CD8+ lymphocytes and CD11c+ putative dendritic cells). A relatively small fraction of IEL (30-50%) expressed alpha 4 beta 7 (mAb Act-1), while most (70%) lamina propria T and B lymphocytes, blasts, plasma cells and macrophages were positive. In GALT, T lymphocytes expressed similar levels of alpha 4 beta 7 as in the lamina propria whereas relatively few B lymphocytes (< 50%) were positive. Isolated lamina propria CD8+, CD4+, CD19+, and CD38+ cells contained mRNA for alpha 4 and the former three subsets as well as appendix CD8+ cells also for beta 7 while only lamina propria CD8+ cells had mRNA for alpha E. Together, the results suggested that alpha E beta 7 and alpha 4 beta 7 are differentially regulated in inductive sites and effector sites of the human gut. Because lymphoid cells at both sites expressed mainly alpha 4 beta 7, this integrin may be a homing receptor on memory and effector cells bound for lamina propria as well as on naive lymphocytes extravasating in GALT. Conversely, because alpha E beta 7 was mainly expressed by CD8+ cells in epithelium and lamina propria, it was probably induced after extravasation, in agreement with the observation that IEL and a fraction of lamina propria T lymphocytes (mainly CD8+ cells) generally expressed higher levels of beta 7 than most CD4+ and B cells. Also a subset of putative dendritic cells located near the follicle-associated epithelium of GALT expressed alpha E beta 7, perhaps reflecting epithelial interaction during primary immune responses.
在人体肠道中研究了参与淋巴细胞黏膜归巢（α4β7）或上皮滞留（αEβ7）的两种替代性整合素。β7亚基（单克隆抗体（mAb）M301）的分布呈双峰型，即αEβ7⁺细胞强烈表达，而α4β7⁺细胞弱表达。超过90%的上皮内淋巴细胞（IEL），包括CD4⁺、T细胞受体（TCR）γ/δ⁺和CD3⁻细胞的次要亚群，以及大多数固有层CD8⁺（88%）和一部分（36%）的CD4⁺淋巴细胞都表达αEβ7。相反，B淋巴细胞系细胞（CD19⁺）和巨噬细胞（CD68⁺）呈阴性。在肠道相关淋巴组织（GALT：派尔集合淋巴结和阑尾）中，只有少数（<5%）细胞αEβ7呈阳性（局限于CD8⁺淋巴细胞和CD11c⁺假定树突状细胞）。相对一小部分IEL（30 - 50%）表达α4β7（mAb Act-1），而大多数（70%）固有层T和B淋巴细胞、母细胞、浆细胞和巨噬细胞呈阳性。在GALT中，T淋巴细胞表达的α4β7水平与固有层相似，而相对较少的B淋巴细胞（<50%）呈阳性。分离的固有层CD8⁺、CD4⁺、CD19⁺和CD38⁺细胞含有α4的mRNA，前三个亚群以及阑尾CD8⁺细胞也含有β7的mRNA，而只有固有层CD8⁺细胞有αE的mRNA。总之，结果表明αEβ7和α4β7在人体肠道的诱导部位和效应部位受到不同的调节。由于两个部位的淋巴细胞主要表达α4β7，这种整合素可能是归巢至固有层的记忆细胞和效应细胞以及在GALT中渗出的幼稚淋巴细胞上的归巢受体。相反，由于αEβ7主要由上皮和固有层中的CD8⁺细胞表达，它可能在渗出后被诱导，这与IEL和一部分固有层T淋巴细胞（主要是CD8⁺细胞）通常比大多数CD4⁺和B细胞表达更高水平的β7这一观察结果一致。此外，位于GALT滤泡相关上皮附近的一部分假定树突状细胞表达αEβ7，这可能反映了初次免疫反应期间的上皮相互作用。
