Chemokine receptor 5 expression in gastric mucosa of Helicobacter pylori-infected and noninfected children

Abstract

Experimental data from human adults or animal models indicate that the Helicobacter pylori-specific immune response is dominated by inflammatory T cells of the Th1 type. To investigate whether a Th1 immune response is established in early H. pylori infection, gastric biopsy samples from 70 children were subjected to immunohistochemical analysis. To this end, T cells, B cells, monocytes, neutrophils, and chemokine receptor 5 (CCR5)-expressing (CCR5(+)) cells, which are associated with Th1 immune responses, were quantified. Children were classified according to H. pylori status and clinical, laboratory, and macroscopic (during endoscopy) findings, without knowledge of histological findings. Group 1 included 31 H. pylori-infected children, group 2 contained 24 children with other conditions possibly affecting the stomach, and group 3 contained 15 children without verifiable pathological findings in the stomach. Lymphoid follicles were present in 90% of biopsy samples from group 1 and 48% of those from group 2 but absent in group 3 biopsy samples. Intraepithelial T cells and CCR5(+) cells were regularly detected in all groups without significant differences. B cells, monocytes, and neutrophils were not found. In contrast, the numbers of lamina propria T cells (P < 0.003) and CCR5(+) cells (P < 0.001) were increased significantly in H. pylori-infected children. B cells (in 13 of 66 children) were detected in children with active (n = 11) or previously cleared (n = 2) H. pylori infections but were absent in healthy children. The numbers of monocytes (in 10 of 67 children) did not differ among the groups. Calculations indicated that the majority of gastric T cells express CCR5; this finding is in contrast to the low percentage of CCR5(+) T cells in the peripheral circulation. Thus, an increase in the numbers of CCR5(+) cells in H. pylori-infected stomach mucosa suggests that this molecule may play an important role in gastric immune responses.

FIG. 1.

Sydney classification for the three patient groups. Bars for each group indicate, from left to right, grades 0, 1, 2, and 3, respectively. Numbers above bars indicate numbers of patients in groups. The asterisk indicates one child who was infected with H. heilmannii but not with H. pylori.

FIG. 2.

Cells per square millimeter in the lamina propria. Bars indicate interquartile ranges.

FIG. 3.

Correlation of CCR5⁺ and CD4⁺ cells in the lamina propria. (Left) Group 1. (Right) Group 3. The Spearman rho test was used.

FIG. 4.

CCR5⁺ T cells in lamina propria (triangles) and peripheral blood (circles) for group 1 (solid line), group 2 (dashed line), and group 3 (dotted line).