Helicobacter pylori vacuolating cytotoxin inhibits activation-induced proliferation of human T and B lymphocyte subsets.
Helicobacter pylori are Gram-negative bacteria that persistently colonize the human gastric mucosa despite the recruitment of immune cells. The H. pylori vacuolating cytotoxin (VacA) recently has been shown to inhibit stimulation-induced proliferation of primary human CD4(+) T cells. In this study, we investigated effects of VacA on the proliferation of various other types of primary human immune cells. Intoxication of PBMC with VacA inhibited the stimulation-induced proliferation of CD4(+) T cells, CD8(+) T cells, and B cells. VacA also inhibited the proliferation of purified primary human CD4(+) T cells that were stimulated by dendritic cells. VacA inhibited both T cell-induced and PMA/anti-IgM-induced proliferation of purified B cells. Intoxication with VacA did not alter the magnitude of calcium flux that occurred upon stimulation of CD4(+) T cells or B cells, indicating that VacA does not alter early signaling events required for activation and proliferation. VacA reduced the mitochondrial membrane potential of CD4(+) T cells, but did not reduce the mitochondrial membrane potential of B cells. We propose that the immunomodulatory actions of VacA on T and B lymphocytes, the major effectors of the adaptive immune response, may contribute to the ability of H. pylori to establish a persistent infection in the human gastric mucosa.
Torres
Victor J
VJ
Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232-2605, USA.
VanCompernolle
Scott E
SE
Sundrud
Mark S
MS
Unutmaz
Derya
D
Cover
Timothy L
TL
D000328:Adult; D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000382:microbiology; D001426:Bacterial Proteins / Q000633:toxicity*; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D015536:Down-Regulation / Q000276:immunology; D006131:Growth Inhibitors / Q000633:toxicity*; D016480:Helicobacter pylori / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D018089:Superantigens / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000382:microbiology; D014617:Vacuoles / Q000276:immunology
D001426:Bacterial Proteins; D006131:Growth Inhibitors; D018089:Superantigens; C074689:VacA protein, Helicobacter pylori