Distribution of β7 integrins in human intestinal mucosa and organized gut‐associated lymphoid tissue

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Abstract
Two alternative integrins involved in mucosal homing (α4β7) or epithelial retention (αEβ7) of lymphocytes were examined in the human gut. The distribution of the β7 subunit [monoclonal antibody (mAb) M301] was bimodal in that it was strongly expressed by αEβ7+ cells but weakly by α4β7+ cells. More than 90% of intraepithelial lymphocytes (IEL), including the minor subsets of CD4+, T‐cell receptor (TCR)γ/δ+, and CD3− cells, expressed αEβ7 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 (Eβ7 (confined to CD8+ lymphocytes and CD11c+ putative dendritic cells). A relatively small fraction of IEL (30–50%) expressed α4β7 (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 α4β7 as in the lamina propria whereas relatively few B lymphocytes (+, CD4+, CD19+, and CD38+ cells contained mRNA for α4 and the former three subsets as well as appendix CD8+ cells also for β7 while only lamina propria CD8+ cells had mRNA for αE. Together, the results suggested that αEβ7 and α4β7 are differentially regulated in inductive sites and effector sites of the human gut. Because lymphoid cells at both sites expressed mainly α4β7, 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 αEβ7 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 β7 than most CD4+ and B cells. Also a subset of putative dendritic cells located near the follicle‐associated epithelium of GALT expressed αEβ7, perhaps reflecting epithelial interaction during primary immune responses.

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