Homing commitment of lymphocytes activated in the human gastric and intestinal mucosa

Abstract

BACKGROUND Gastric infection with the human pathogen Helicobacter pylori results in a large accumulation of IgA and IgM secreting cells in the gastric mucosa. The molecular mechanisms resulting in B cell migration to the gastric mucosa in H pylori infection are however not known.

AIMS To examine expression of the mucosal homing receptor integrin α4β7 and the homing receptor for secondary lymphoid tissues, l-selectin, on lymphocytes activated by gastric, intestinal, or systemic antigens. Furthermore, to examine gastric expression of the mucosal addressin cellular adhesion molecule 1 (MAdCAM-1), the endothelial counter-receptor to integrin α4β7.

SUBJECTS AND METHODS H pylori infected individuals were immunised by either gastric (n=8) or intestinal (n=8) delivery of an inactivated cholera vaccine. The resulting circulating vaccine specific B cells were sorted according to α4β7 and l-selectin expression and assayed for production of IgA and IgG using an enzyme linked immunospot assay. In addition, circulating CD4+ T cells from seven H pylori infected individuals were fractionated according to α4β7 and l-selectin expression. The resulting T cell fractions were then assayed for specific proliferation againstH pylori or the systemic antigen tetanus toxoid. Finally, gastric expression of MAdCAM-1 was determined by immunohistochemistry in H pylori infected (n=16) and uninfected (n=8) individuals.

RESULTS Virtually all B cells induced by both gastric and intestinal antigen delivery expressed α4β7 whereas less then half coexpressedl-selectin. Furthermore, H pylori reactive T cells were mainly found in the α4β7+l-selectin+ T cell fraction whereas tetanus specific T cells were largely α4β7−l-selectin+. MAdCAM-1 was present in similar amounts in gastric mucosa fromH pylori infected and uninfected individuals.

CONCLUSIONS B cells and T cells activated by antigens delivered to the gastric mucosa express the mucosal homing receptor integrin α4β7, as do cells activated in the intestine. Together with the observation that gastric endothelial cells express MAdCAM-1, this may partly explain the homing of lymphocytes activated in the stomach or in the small intestine to the gastric mucosa.