News Release

Gut bacteria tire out T cells

Peer-Reviewed Publication

Rockefeller University Press

Leaky intestines may cripple bacteria-fighting immune cells in patients with a rare hereditary disease, according to a study by researchers in Lausanne, Switzerland. The study, published in The Journal of Experimental Medicine on September 15, may explain why these patients suffer from recurrent bacterial infections.

Patients with a disease called common variable immunodeficiency (CVID) suffer from recurrent bacterial infections as a result of faulty immune cells. But despite these immune defects, CVID patients rarely contract viral infections. New data from Matthieu Perreau and colleagues in Lausanne now show that bacteria-fighting T cells in the blood of these patients showed signs of exhaustion (evident by their expression of an inhibitory protein called PD-1), but virus-fighting T cells were unscathed.

T cell exhaustion in the patients was associated with increased gut bacteria in the bloodstream, possibly due to the lack of protective antibodies that normally clear these wayward bugs. As a result, bacteria-specific T cells may be repetitively stimulated, a scenario known to trigger exhaustion. Indeed, the tired T cells from CVID patients could be rejuvenated by blocking PD-1. And in patients who received infusions of antibodies ("IVIG" therapy), often used to treat symptoms of CVID, PD-1 expression on T cells waned along with the levels of bacteria in the blood.

The data suggest that "immunotherapy" strategies aimed at perking up T cells—already in use in cancer patients—may protect CVID patients against recurrent bacterial infection.

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Perreau, M., et al. 2014. J. Exp. Med. doi:10.1084/jem.20140039

About The Journal of Experimental Medicine

The Journal of Experimental Medicine (JEM) is published by The Rockefeller University Press. All editorial decisions on manuscripts submitted are made by active scientists in conjunction with our in-house scientific editors. JEM content is posted to PubMed Central, where it is available to the public for free six months after publication. Authors retain copyright of their published works and third parties may reuse the content for non-commercial purposes under a creative commons license. For more information, please visit http://www.jem.org .


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