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

人类胃和肠粘膜中激活的淋巴细胞的归巢定型

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作者:M Quiding-Järbrink, I Ahlstedt, C Lindholm, E L Johansson, H Lönroth

Aims

To examine expression of the mucosal homing receptor integrin alpha4beta7 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 alpha4beta7. Subjects and

Background

Gastric infection with the human pathogen Helicobacter pylori

Conclusions

B cells and T cells activated by antigens delivered to the gastric mucosa express the mucosal homing receptor integrin alpha4beta7, 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.

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 alpha4beta7 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 alpha4beta7 and L-selectin expression. The resulting T cell fractions were then assayed for specific proliferation against H 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 alpha4beta7 whereas less then half coexpressed L-selectin. Furthermore, H pylori reactive T cells were mainly found in the alpha4beta7+L-selectin+ T cell fraction whereas tetanus specific T cells were largely alpha4beta7-L-selectin+. MAdCAM-1 was present in similar amounts in gastric mucosa from H 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 alpha4beta7, 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.

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