Helicobacter pylori-specific CD4+ T cells home to and accumulate in the human Helicobacter pylori-infected gastric mucosa.
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.
Lundgren
Anna
A
Department of Medical Microbiology and Immunology, Göteborg University, 40530 Göteborg, Sweden. anna.lundgren@microbio.gu.se
Trollmo
Christina
C
Edebo
Anders
A
Svennerholm
Ann-Mari
AM
Lundin
B Samuel
BS
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000382:microbiology; D002449:Cell Aggregation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D018925:Chemokines / Q000096:biosynthesis; D005260:Female; D005753:Gastric Mucosa / Q000276:immunology* / Q000382:microbiology; D016481:Helicobacter Infections / Q000276:immunology*; D016480:Helicobacter pylori / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D054397:Receptors, CCR3; D019713:Receptors, CCR5 / Q000096:biosynthesis; D019707:Receptors, Chemokine / Q000096:biosynthesis; D016201:Receptors, Lymphocyte Homing / Q000096:biosynthesis
C515350:CCR3 protein, human; D018925:Chemokines; D054397:Receptors, CCR3; D019713:Receptors, CCR5; D019707:Receptors, Chemokine; D016201:Receptors, Lymphocyte Homing