{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T10:07:32Z","timestamp":1789380452983,"version":"build-2803163510"},"reference-count":56,"publisher":"Rockefeller University Press","issue":"10","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2014,9,22]]},"abstract":"<jats:p>In the present study, we have investigated the functional profile of CD4 T cells from patients with common variable immunodeficiency (CVID), including production of cytokines and proliferation in response to bacteria and virus-derived antigens. We show that the functional impairment of CD4 T cells, including the reduced capacity to proliferate and to produce IFN-\u03b3 and IL-2, was restricted to bacteria-specific and not virus-specific CD4 T cells. High levels of endotoxins were found in the plasma of patients with CVID, suggesting that CD4 T cell dysfunction might be caused by bacterial translocation. Of note, endotoxemia was associated with significantly higher expression of programmed death 1 (PD-1) on CD4 T cells. The blockade of the PD-1\u2013PD-L1\/2 axis in vitro restored CD4 T cell proliferation capacity, thus indicating that PD-1 signaling negatively regulates CD4 T cell functions. Finally, we showed that intravenous immunoglobulin G (IVIG) treatment significantly reduced endotoxemia and the percentage of PD-1+ CD4 T cells, and restored bacteria-specific CD4 T cell cytokine production and proliferation. In conclusion, the present study demonstrates that the CD4 T cell exhaustion and functional impairment observed in CVID patients is associated with bacterial translocation and that IVIG treatment resolves bacterial translocation and restores CD4 T cell functions.<\/jats:p>","DOI":"10.1084\/jem.20140039","type":"journal-article","created":{"date-parts":[[2014,9,16]],"date-time":"2014-09-16T07:56:27Z","timestamp":1410854187000},"page":"2033-2045","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":113,"title":["Exhaustion of bacteria-specific CD4 T cells and microbial translocation in common variable immunodeficiency disorders"],"prefix":"10.1084","volume":"211","author":[{"given":"Matthieu","family":"Perreau","sequence":"first","affiliation":[{"name":"Service of Immunology and Allergy 1 and 2"},{"name":"Service of Infectious Diseases, Department of Medicine, Lausanne University Hospital, University of Lausanne, 1011 Lausanne, 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