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IL-27, a member of the IL-6\/IL-12 cytokine family, has been shown to promote development of IL-10\u2013producing T cells, in part by upregulating their production of autocrine IL-21. We investigated whether IL-27 and IL-21 are associated with human VL. IL-27 was elevated in VL plasma, and at pretreatment, spleen cells showed significantly elevated mRNA levels of both IL-27 subunits, IL-27p28 and EBI-3, as well as IL-21, compared with posttreatment biopsies. CD14+ spleen cells were the main source of IL-27 mRNA, whereas CD3+ T cells were the main source of IL-21. IL-27 mRNA could be strongly upregulated in normal donor macrophages with IFN-\u03b3 and IL-1\u03b2, conditions consistent with those in the VL spleen. Last, a whole-blood assay revealed that most VL patients could produce Ag-specific IFN-\u03b3 and IL-10 and that the IL-10 could be augmented with recombinant human IL-21. Thus, proinflammatory cytokines acting on macrophages in the VL spleen have the potential to upregulate IL-27, which in turn can induce IL-21 to expand IL-10\u2013producing T cells as a mechanism of feedback control.<\/jats:p>","DOI":"10.4049\/jimmunol.1003588","type":"journal-article","created":{"date-parts":[[2011,3,1]],"date-time":"2011-03-01T16:11:07Z","timestamp":1298995867000},"page":"3977-3985","source":"Crossref","is-referenced-by-count":129,"title":["IL-27 and IL-21 Are Associated with T Cell IL-10 Responses in Human Visceral Leishmaniasis"],"prefix":"10.1093","volume":"186","author":[{"given":"Nasim Akhtar","family":"Ansari","sequence":"first","affiliation":[{"name":"Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"},{"name":"Infectious Disease Research Laboratory, Department of Medicine, Institute of Medical Sciences, Banaras Hindu University , Varanasi 221005 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajiv","family":"Kumar","sequence":"additional","affiliation":[{"name":"Infectious Disease Research Laboratory, Department of Medicine, Institute of Medical Sciences, Banaras Hindu University , Varanasi 221005 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shalini","family":"Gautam","sequence":"additional","affiliation":[{"name":"Infectious Disease Research Laboratory, Department of Medicine, Institute of Medical Sciences, Banaras Hindu University , Varanasi 221005 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Nyl\u00e9n","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet , SE-171 77 Stockholm ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Om Prakash","family":"Singh","sequence":"additional","affiliation":[{"name":"Infectious Disease Research Laboratory, Department of Medicine, Institute of Medical Sciences, Banaras Hindu University , Varanasi 221005 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shyam","family":"Sundar","sequence":"additional","affiliation":[{"name":"Infectious Disease Research Laboratory, Department of Medicine, Institute of Medical Sciences, Banaras Hindu University , Varanasi 221005 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Sacks","sequence":"additional","affiliation":[{"name":"Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2011,4,1]]},"reference":[{"key":"2025032411193279200_r1","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1016\/S1473-3099(02)00347-X","article-title":"Visceral leishmaniasis: current status of control, diagnosis, and treatment, and a proposed research and development agenda","volume":"2","author":"Guerin","year":"2002","journal-title":"Lancet Infect. 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