Modulation of the CD4+ T-Cell Response by Helicobacter pylori Depends on Known Virulence Factors and Bacterial Cholesterol and Cholesterol α-Glucoside Content

Helicobacter pylori blocks the proliferation of human CD4(+) T cells, facilitated by vacuolating exotoxin (VacA) and gamma-glutamyl transpeptidase (GGT). H. pylori-triggered T-cell reactions in mice correlate with bacterial cholesterol and cholesterol alpha-glucoside content but their role in human cells is unclear. We characterized the effect of VacA, GGT, and cholesterol on T-helper 1, T-helper 2, T-regulatory and T-helper 17 associated cytokines and T-cell proliferation. VacA, GGT, and bacterial cholesterol content exhibited differential and synergistic inhibitory effects on the expression of activation markers CD25 and CD69 and on interleukin 2, interleukin 4, interleukin 10, and interferon gamma production. These factors did not affect the H. pylori-mediated abrogation of transforming growth factor beta secretion or increased interleukin 6 production. Cholesterol alpha-glucosyltransferase-deficient bacteria exerted strongly reduced antiproliferative effects on primary human CD4(+) T cells. In conclusion, H. pylori shapes rather than suppresses human CD4(+) T-cell responses, and glucosylated cholesterol is a relevant bacterial component involved in this modulation.