Filarial lymphedema is characterized by antigen-specific Th1 and th17 proinflammatory responses and a lack of regulatory T cells.

PLoS Negl Trop Dis 2009 21;3(4):e420. Epub 2009 Apr 21.

National Institutes of Health-International Center for Excellence in Research, Chennai, India.

Background: Lymphatic filariasis can be associated with development of serious pathology in the form of lymphedema, hydrocele, and elephantiasis in a subset of infected patients.

Methods And Findings: To elucidate the role of CD4(+) T cell subsets in the development of lymphatic pathology, we examined specific sets of cytokines in individuals with filarial lymphedema in response to parasite antigen (BmA) and compared them with responses from asymptomatic infected individuals. We also examined expression patterns of Toll-like receptors (TLR1-10) and Nod-like receptors (Nod1, Nod2, and NALP3) in response to BmA. BmA induced significantly higher production of Th1-type cytokines-IFN-gamma and TNF-alpha-in patients with lymphedema compared with asymptomatic individuals. Notably, expression of the Th17 family of cytokines-IL-17A, IL-17F, IL-21, and IL-23-was also significantly upregulated by BmA stimulation in lymphedema patients. In contrast, expression of Foxp3, GITR, TGFbeta, and CTLA-4, known to be expressed by regulatory T cells, was significantly impaired in patients with lymphedema. BmA also induced significantly higher expression of TLR2, 4, 7, and 9 as well Nod1 and 2 mRNA in patients with lymphedema compared with asymptomatic controls.

Conclusion: Our findings implicate increased Th1/Th17 responses and decreased regulatory T cells as well as regulation of Toll- and Nod-like receptors in pathogenesis of filarial lymphedema.

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http://dx.doi.org/10.1371/journal.pntd.0000420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2666805PMC
February 2010
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References

(Supplied by CrossRef)
Predominant CD8+ infiltrate in limb biopsies of individuals with filarial lymphedema and elephantiasis.
DO Freedman et al.
Am J Trop Med Hyg 1995
Biased TCR repertoire in infiltrating lesional T cells in human bancroftian filariasis.
DO Freedman et al.
J Immunol 1999
Very late antigen-4/vascular cell adhesion molecule-1 (VLA-4/VCAM-1) pathway is involved in the transendothelial migration of lymphocytes in bancroftian filariasis.
DO Freedman et al.
J Immunol 1996
Lymphocyte subpopulations in bancroftian filariasis: activated (DR+) CD8+ T cells in patients with chronic lymphatic obstruction.
RB Lal et al.
Clin Exp Immunol 1989

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