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

Abstract

Two alternative integrins involved in mucosal homing (α₄β₇) or epithelial retention (α_Eβ₇) 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 α_Eβ₇⁺ 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 α_Eβ₇ 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 α_E. Together, the results suggested that α_Eβ₇ 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 α_Eβ₇ 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 α_Eβ₇, perhaps reflecting epithelial interaction during primary immune responses.