NDLI: Splenic accumulation of IL-10 mRNA in T cells distinct from CD4+CD25+ (Foxp3) regulatory T cells in human visceral leishmaniasis

Content Provider	PubMed Central
Author	Nylén, Susanne Maurya, Radheshyam Eidsmo, Liv Manandhar, Krishna Das Sundar, Shyam Sacks, David
Abstract	Visceral leishmaniasis (VL) is a life-threatening disease characterized by uncontrolled parasitization of the spleen, liver, and bone marrow. Interleukin (IL)-10 has been implicated in the suppression of host immunity in human VL based on the elevated levels of IL-10 observed in plasma and lesional tissue, and its role in preventing clearance of Leishmania donovani in murine models of VL. The aim of this study was to identify the cellular source of IL-10 in human VL and determine if CD4+CD25+ (Foxp3high) regulatory T (T reg) cells are associated with active disease. We analyzed surface marker and gene expression in peripheral blood mononuclear cells and splenic aspirates from Indian VL patients before and 3–4 wk after treatment with Amphotericin B. The results did not point to an important role for natural CD4+CD25+ (Foxp3high) T reg cells in human VL. They did not accumulate in and were not a major source of IL-10 in the spleen, and their removal did not rescue antigen-specific interferon γ responses. In contrast, splenic T cells depleted of CD25+ cells expressed the highest levels of IL-10 mRNA and were the predominant lymphocyte population in the VL spleen. The elevated levels of IL-10 in VL plasma significantly enhanced the growth of L. donovani amastigotes in human macrophages. The data implicate IL-10–producing CD25−Foxp3− T cells in the pathogenesis of human VL.
Related Links	http://dx.doi.org/10.1084/jem.20061141
Ending Page	817
Page Count	13
Starting Page	805
File Format	PDF
ISSN	00221007
e-ISSN	15409538
Journal	The Journal of Experimental Medicine
Issue Number	4
Volume Number	204
Language	English
Publisher	The Rockefeller University Press
Publisher Date	2007-04-16
Access Restriction	Open
Rights Holder	The Rockefeller University Press
Subject Keyword	Immunology Immunology and Allergy Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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