IL-27 and IL-21 are associated with T cell IL-10 responses in human visceral leishmaniasis

Ansari, Nasim Akhtar ; Kumar, Rajiv ; Gautam, Shalini ; Nylén, Susanne ; Singh, Om Prakash ; Sundar, Shyam ; Sacks, David (2011) IL-27 and IL-21 are associated with T cell IL-10 responses in human visceral leishmaniasis The Journal of Immunology, 186 (7). pp. 3977-3985. ISSN 0022-1767

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Official URL: http://www.jimmunol.org/content/186/7/3977.long

Related URL: http://dx.doi.org/10.4049/jimmunol.1003588

Abstract

IL-10 is believed to underlie many of the immunologic defects in human visceral leishmaniasis (VL). We have identified CD4+CD25Foxp3 T cells as the major source of IL-10 in the VL spleen. IL-27, a member of the IL-6/IL-12 cytokine family, has been shown to promote development of IL-10–producing 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-γ and IL-1β, conditions consistent with those in the VL spleen. Last, a whole-blood assay revealed that most VL patients could produce Ag-specific IFN-γ 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–producing T cells as a mechanism of feedback control.

Item Type:Article
Source:Copyright of this article belongs to American Association of Immunologists.
ID Code:94509
Deposited On:17 Sep 2012 11:57
Last Modified:17 Sep 2012 11:57

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