Helicobacter pylori-Specific CD4⁺ T Cells Home to and Accumulate in the Human Helicobacter pylori-Infected Gastric Mucosa

• Published in: Infection and Immunity Vol. 73; no. 9; pp. 5612 - 5619
• Main Authors: Lundgren, Anna, Trollmo, Christina, Edebo, Anders, Svennerholm, Ann-Mari, Lundin, B. Samuel
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for Microbiology 01.09.2005
• Subjects: Adult; antigens; bacteria; Bacteriology; Biological and medical sciences; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - microbiology; Cell Aggregation - immunology; cell culture; Cell Movement - immunology; chemokines; Chemokines - biosynthesis; cross reaction; duodenum; Female; Fundamental and applied biological sciences. Psychology; gastric mucosa; Gastric Mucosa - immunology; Gastric Mucosa - microbiology; Helicobacter Infections - immunology; Helicobacter pylori; Helicobacter pylori - immunology; Host Response and Inflammation; Humans; interleukin-2; interleukin-7; Male; Microbiology; Middle Aged; Miscellaneous; receptors; Receptors, CCR3; Receptors, CCR5 - biosynthesis; Receptors, Chemokine - biosynthesis; Receptors, Lymphocyte Homing - biosynthesis; T-lymphocytes; Human; Infection; Spirillales; Helicobacter pylori; Microbiology; Mucosa; T-Lymphocyte; Spirillaceae; Bacteria; Immunity
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.73.9.5612-5619.2005

Helicobacter pylori infects the stomach and duodenal mucosa. T cells are important components of the H. pylori-induced immune response, but little is currently known about how these cells are recruited to the infected mucosa. Here, we have characterized stomach and duodenal T cells isolated from H. pylori-infected and noninfected subjects with regard to subtype, expression of homing and chemokine receptors, and in vitro reactivity to H. pylori antigens. Higher numbers of CD4⁺ but similar numbers of CD8⁺ lamina propria T cells were isolated from stomach biopsies from H. pylori-positive compared to H. pylori-negative individuals. CD4⁺ T cells from infected stomach expressed increased levels of the homing receptor L-selectin and the chemokine receptor CCR4 compared to CD4⁺ T cells from uninfected stomach. Infected stomach mucosa also contained increased levels of the CCR4 chemokine ligand MDC/CCL22. In contrast, comparable numbers of CD4⁺ T cells with similar receptor expression were isolated from the duodenum of H. pylori-positive and H. pylori-negative individuals. In vitro proliferation of mucosal T cells was strongly enhanced by the addition of interleukin-2 (IL-2) and IL-7 to the cell cultures. Using this approach, H. pylori-specific T-cell responses were detected in stomach CD4⁺ T cells from H. pylori-positive but not H. pylori-negative individuals. Duodenal T cells from only a few individuals responded to H. pylori stimulation, and the responsiveness was not restricted to H. pylori-positive individuals, suggesting limited H. pylori specificity in the duodenum and possible cross-reactivity with antigens from other bacteria in this compartment. In conclusion, these results suggest that H. pylori-specific CD4⁺ T cells preferentially home to and accumulate in the infected stomach and that L-selectin and CCR4/MDC are important for this recruitment.