{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T16:35:51Z","timestamp":1775147751066,"version":"3.50.1"},"reference-count":68,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2013,4,1]],"date-time":"2013-04-01T00:00:00Z","timestamp":1364774400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The breakdown of l-arginine to ornithine and urea by host arginase supports Leishmania proliferation in macrophages. Studies using arginase-null mutants show that Leishmania-derived arginase plays an important role in disease pathogenesis. We investigated the role of parasite-derived arginase in secondary (memory) anti-Leishmania immunity in the resistant C57BL\/6 mice. We found that C57BL\/6 mice infected with arginase-deficient (arg\u2212) L. major failed to completely resolve their lesion and maintained chronic pathology after 16 wk, a time when the lesion induced by wild-type L. major is completely resolved. This chronic disease was associated with impaired Ag-specific proliferation and IFN-\u03b3 production, a concomitant increase in programmed cell death-1 (PD-1) expression on CD4+ T cells, and failure to induce protection against secondary L. major challenge. Treatment with anti\u2013PD-1 mAb restored T cell proliferation and IFN-\u03b3 production in vitro and led to complete resolution of chronic lesion in arg\u2212\u2008L. major\u2013infected mice. These results show that infection with arg\u2212\u2008L. major results in chronic disease due in part to PD-1\u2013mediated clonal exhaustion of T cells, suggesting that parasite-derived arginase contributes to the overall quality of the host immune response and subsequent disease outcome in L. major\u2013infected mice. They also indicate that persistent parasites alone do not regulate the quality of secondary anti-Leishmania immunity in mice and that the quality of the primary immune response may be playing a hitherto unrecognized dominant role in this process.<\/jats:p>","DOI":"10.4049\/jimmunol.1202537","type":"journal-article","created":{"date-parts":[[2013,3,5]],"date-time":"2013-03-05T11:06:38Z","timestamp":1362481598000},"page":"3380-3389","source":"Crossref","is-referenced-by-count":42,"title":["Parasite-Derived Arginase Influences Secondary Anti-<i>Leishmania<\/i> Immunity by Regulating Programmed Cell Death-1\u2013Mediated CD4+ T Cell Exhaustion"],"prefix":"10.1093","volume":"190","author":[{"given":"Zhirong","family":"Mou","sequence":"first","affiliation":[{"name":"Department of Immunology, University of Manitoba , Winnipeg, Manitoba R3E 0T5,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helen M","family":"Muleme","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Manitoba , Winnipeg, Manitoba R3E 0T5,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Manitoba , Winnipeg, Manitoba R3E 0T5,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Manitoba , Winnipeg, Manitoba R3E 0T5,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ifeoma B","family":"Okwor","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, University of Manitoba , Winnipeg, Manitoba R3E 0T5,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiby M","family":"Kuriakose","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Manitoba , Winnipeg, Manitoba R3E 0T5,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen M","family":"Beverley","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology, Washington University School of Medicine , St. Louis, MO 63110"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jude E","family":"Uzonna","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Manitoba , Winnipeg, Manitoba R3E 0T5,","place":["Canada"]},{"name":"Department of Medical Microbiology, University of Manitoba , Winnipeg, Manitoba R3E 0T5,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2013,4,1]]},"reference":[{"key":"2025032406464387500_r1","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1086\/382135","article-title":"Persistence of leishmania parasites in scars after clinical cure of American cutaneous leishmaniasis: is there a sterile cure?","volume":"189","author":"Mendon\u00e7a","year":"2004","journal-title":"J. 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