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

Abstract

IL-10 is believed to underlie many of the immunologic defects in human visceral leishmaniasis (VL). We have identified CD4(+)CD25(-)Foxp3(-) 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.

• Authors: Nasim Akhtar Ansari, Rajiv Kumar, Shalini Gautam, Susanne Nylén, Om Prakash Singh, Shyam Sundar, David Sacks
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 186 Issue 7 Pg. 3977-85 (Apr 01 2011) ISSN: 1550-6606 [Electronic] United States
• PMID: 21357266 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)

Chemical References

• IL10 protein, human
• Interleukin-17
• Interleukins
• MYDGF protein, human
• RNA, Messenger
• Interleukin-10
• interleukin-21

Topics

• Adult
• Feedback, Physiological (physiology)
• Female
• Humans
• Interleukin-10 (biosynthesis, blood, physiology)
• Interleukin-17 (biosynthesis, blood)
• Interleukins (biosynthesis, blood, physiology)
• Leishmaniasis, Visceral (blood, immunology, metabolism)
• Macrophages (immunology, metabolism, pathology)
• Male
• RNA, Messenger (biosynthesis)
• Spleen (immunology, metabolism)
• T-Lymphocytes (immunology, metabolism, pathology)
• T-Lymphocytes, Helper-Inducer (immunology, metabolism, pathology)
• Up-Regulation (immunology)
• Young Adult