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Gastroenterology. 2005 May;128(5):1327-39.

A secreted low-molecular-weight protein from Helicobacter pylori induces cell-cycle arrest of T cells.

Author information

1
Department of Medicine II, Technical University, Munich, Germany.

Abstract

BACKGROUND & AIMS:

Although Helicobacter pylori is recognized by the human immune system, the bacteria are not eliminated and lead to a chronic inflammation of the gastric mucosa.

METHODS:

We investigated the interaction of H. pylori with human lymphocytes. T and B lymphocytes were isolated from H. pylori-infected patients and stimulated with anti-CD3/CD28 or interleukin-6.

RESULTS:

Proliferation of lymphocytes was abolished on co-incubation with different H. pylori strains (1-5 bacteria/cell) or with protein extracts of culture supernatants. Inhibition of proliferation was independent of known virulence factors. The factor is a protein or protein complex with an apparent molecular weight between 30 and 60 kilodaltons, clearly distinct from VacA. Although antigen-specific activation of T cells (as shown by nuclear factor of activated T cells [NFAT]-activation, interferon-gamma production, and CD25 or CD69 up-regulation) remained intact, cell-cycle analysis showed that S-phase entry of T cells was inhibited completely by H. pylori. Consequently, stimulated T cells arrested in the G1 phase of the cell cycle. Western blot analysis showed markedly reduced phosphorylation of the retinoblastoma protein (pRb), suggesting inhibition of G1 cyclin-dependent kinase activity. In line with this, activities of cyclin D3 and cyclin E were down-regulated, and levels of the cyclin-dependent kinase inhibitor p27Kip1 were increased. Mouse embryonic fibroblasts deficient in p27 showed a decrease in H. pylori-induced inhibition of cell proliferation, suggesting a central role for p27 in mediating H. pylori-induced G1 arrest.

CONCLUSIONS:

Induction of cell-cycle arrest in lymphocytes may be of major significance for the chronic persistence of bacteria in the human stomach.

PMID:
15887115
[Indexed for MEDLINE]

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