{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T21:18:53Z","timestamp":1789852733528,"version":"4.0.1"},"reference-count":60,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2015,12,1]],"date-time":"2015-12-01T00:00:00Z","timestamp":1448928000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:named-content content-type=\"genus-species\">Brucella melitensis<\/jats:named-content>\n            is a well-adapted zoonotic pathogen considered a scourge of mankind since recorded history. In some cases, initial infection leads to chronic and reactivating brucellosis, incurring significant morbidity and economic loss. The mechanism by which\n            <jats:named-content content-type=\"genus-species\">B. melitensis<\/jats:named-content>\n            subverts adaptive immunological memory is poorly understood. Previous work has shown that\n            <jats:named-content content-type=\"genus-species\">Brucella<\/jats:named-content>\n            -specific CD8\n            <jats:sup>+<\/jats:sup>\n            T cells express gamma interferon (IFN-\u03b3) and can transition to long-lived memory cells but are not polyfunctional. In this study, chronic infection of mice with\n            <jats:named-content content-type=\"genus-species\">B. melitensis<\/jats:named-content>\n            led to CD8\n            <jats:sup>+<\/jats:sup>\n            T cell exhaustion, manifested by programmed cell death 1 (PD-1) and lymphocyte activation gene 3 (LAG-3) expression and a lack of IFN-\u03b3 production. The\n            <jats:named-content content-type=\"genus-species\">B. melitensis<\/jats:named-content>\n            -specific CD8\n            <jats:sup>+<\/jats:sup>\n            T cells that produced IFN-\u03b3 expressed less IFN-\u03b3 per cell than did CD8\n            <jats:sup>+<\/jats:sup>\n            cells from uninfected mice. Both memory precursor (CD8\n            <jats:sup>+<\/jats:sup>\n            LFA1\n            <jats:sup>HI<\/jats:sup>\n            CD127\n            <jats:sup>HI<\/jats:sup>\n            KLRG1\n            <jats:sup>LO<\/jats:sup>\n            ) and long-lived memory (CD8\n            <jats:sup>+<\/jats:sup>\n            CD27\n            <jats:sup>HI<\/jats:sup>\n            CD127\n            <jats:sup>HI<\/jats:sup>\n            KLRG1\n            <jats:sup>LO<\/jats:sup>\n            ) cells were identified during chronic infection. Interestingly, after adoptive transfer, mice receiving cells from chronically infected animals were able to contain infection more rapidly than recipients of cells from acutely infected or uninfected donors, although the proportions of exhausted CD8\n            <jats:sup>+<\/jats:sup>\n            T cells increased after adoptive transfer in both challenged and unchallenged recipients. CD8\n            <jats:sup>+<\/jats:sup>\n            T cells of challenged recipients initially retained the stunted IFN-\u03b3 production found prior to transfer, and cells from acutely infected mice were never seen to transition to either memory subset at all time points tested, up to 30 days post-primary infection, suggesting a delay in the generation of memory. Here we have identified defects in\n            <jats:named-content content-type=\"genus-species\">Brucella<\/jats:named-content>\n            -responsive CD8\n            <jats:sup>+<\/jats:sup>\n            T cells that allow chronic persistence of infection.\n          <\/jats:p>","DOI":"10.1128\/iai.01184-15","type":"journal-article","created":{"date-parts":[[2015,9,29]],"date-time":"2015-09-29T02:18:33Z","timestamp":1443493113000},"page":"4759-4771","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":45,"title":["CD8\n            <sup>+<\/sup>\n            T Cell Exhaustion, Suppressed Gamma Interferon Production, and Delayed Memory Response Induced by Chronic Brucella melitensis Infection"],"prefix":"10.1128","volume":"83","author":[{"given":"Marina","family":"Durward-Diioia","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Midwestern University, Glendale, Arizona, USA"},{"name":"Department of Pathobiological Sciences, University of Wisconsin\u2014Madison School of Veterinary Medicine, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerome","family":"Harms","sequence":"additional","affiliation":[{"name":"Department of Pathobiological Sciences, University of Wisconsin\u2014Madison School of Veterinary Medicine, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mike","family":"Khan","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Pathology Training Program, University of Wisconsin\u2014Madison School of Medicine and Public Health, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cherisse","family":"Hall","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Wisconsin\u2014Madison School of Medicine and Public Health, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith A.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Wisconsin\u2014Madison School of Medicine and Public Health, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary A.","family":"Splitter","sequence":"additional","affiliation":[{"name":"Department of Pathobiological Sciences, University of Wisconsin\u2014Madison School of Veterinary Medicine, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2009.0067"},{"key":"e_1_3_3_3_2","volume-title":"Report of a joint WHO\/DFID-AHP meeting with the participation of FAO and OIE","author":"Maudlin I","year":"2005","unstructured":"Maudlin I, Weber-Mosdorf S. 2005. 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