[The evaluation of cagA and other vaccine candidate proteins of Helicobacter pylori on T cell apoptosis mediated by Fas/Fas ligand interaction].
OBJECTIVE
To evaluate the effect of several surface proteins of Helicobacter pylori (H. pylori) on inducing apoptosis of T cells through the modulation of Fas/Fas ligand (FasL) interaction and to provide information on the screen of safe and effective immunogen for H. pylori vaccine.


METHODS
T cell apoptosis induced by cagA+ and isogenic cagA knockout strain, recombinant urease, HpaA and outer membrane proteins, Hop25, Hop35 and Hop38 was detected by JAM assay. Flow cytometry was used to evaluate the increase in FasL expression on T cells under the stimulation of these bacterial proteins. Metalloprotease inhibitor, 1, 10-Phenanthroline (PHE) and protein synthesis inhibitor, emetine, were used to change the activity of FasL to confirm the association of FasL with H. pylori mediated killing toward T cells.


RESULTS
The effect of cagA+ H. pylori was stronger in both the induction of apoptosis and FasL expression of T cells than that of cagA knockout strain. H. pylori urease could not kill T cell, while Hop38 had the strongest effect among the tested H. pylori proteins on the induction of T cell apoptosis through increasing FasL expression. Metaloprotease inhibitor could increase the killing of T cells induced by H. pylori because of its ability to prevent the cleavage of membrane-bound FasL protein. On the other hand, emetine could decrease H. pylori mediated killing by inhibiting of FasL synthesis on T cells.


CONCLUSIONS
cagA and Hop38 protein might be involved in the negative regulation of T cell growth through upregulating FasL expression urease and other Hop proteins tested might be safe and effective to be used as the antigens for H. pylori vaccine.
Wang
J
J
PLA Institute for Digestive Disease, Nanfang Hospital, First Military Medical University, Guangzhou 510515, China.
Chen
Y
Y
Lai
Z
Z
D000942:Antigens, Bacterial; D017209:Apoptosis; D001426:Bacterial Proteins / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology*; D053222:Fas Ligand Protein; D016480:Helicobacter pylori / Q000276:immunology*; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; C080866:cagA protein, Helicobacter pylori