Helicobacter pylori-induced apoptosis in T cells is mediated by the mitochondrial pathway independent of death receptors.
BACKGROUND
Chronic infection with Helicobacter pylori is related to the pathogenesis of the noncardia carcinoma of the stomach. In this study we investigated the mechanisms of H. pylori-induced apoptosis in T lymphocytes, which could explain a mechanism of immune evasion facilitating chronic inflammation of the mucosa and gastric carcinogenesis.


METHODS
The supernatant of H. pylori culture was used to study the mechanism of apoptosis induction in human leukaemia T cell lines Jurkat and CEM and in primary T cells. The cytotoxin associated gene A (CagA) and vacuolating cytotoxin A (Vac A) positive bacterial strain H. pylori 60190 (CagA(+), VacA(+)) and as a control the less toxic H. pylori strain Tx30a (CagA(-), VacA(-)) were used to produce the supernatant. Cell death was determined by DNA fragmentation and protein expression by Western blot.


RESULTS
H. pylori 60190-induced apoptosis was neither blocked by inhibition of the death ligands TRAIL (TNF-related apoptosis-inducing ligand), CD95L/FasL and TNF-alpha (tumour necrosis factor-a) in wild type Jurkat cells nor in FADD(def) (Fas-associated death domain protein) and caspase-8(def) subclones of the Jurkat cell line. Yet, the pancaspase inhibitor zVAD-fmk could inhibit up to 90% of H. pylori-induced apoptosis. Stable transfection of Jurkat wild type cells with Bcl-x(L and) Bcl-2 resulted in marked reduction of H. pylori-induced apoptosis, showing that the mitochondrial pathway is the key regulator. This is supported by the finding that surviving primary human lymphocytes upregulate Bcl-2 when exposed to H. pylori supernatant.


CONCLUSIONS
H. pylori-induced apoptosis of T cells is mediated by the mitochondrial pathway and could create a local environment that facilitates life-long infection by immune evasion.
Ganten
T M
TM
University of Heidelberg, Germany. Tom.Ganten@med.uni-heidelberg.de
Aravena
E
E
Sykora
J
J
Koschny
R
R
Mohr
J
J
Rudi
J
J
Stremmel
W
W
Walczak
H
H
D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D002908:Chronic Disease; D016481:Helicobacter Infections / Q000150:complications*; D016480:Helicobacter pylori; D006801:Humans; D015458:Leukemia, T-Cell / Q000382:microbiology*; D008928:Mitochondria / Q000382:microbiology*; D013601:T-Lymphocytes / Q000382:microbiology*