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Removal of Regulatory T Cell Activity Reverses Hyporesponsiveness and Leads to Filarial Parasite
 

Summary: Removal of Regulatory T Cell Activity Reverses
Hyporesponsiveness and Leads to Filarial Parasite
Clearance In Vivo1
Matthew D. Taylor, Laetitia LeGoff, Anjanette Harris, Eva Malone,2
Judith E. Allen, and
Rick M. Maizels3
Human filarial parasites cause chronic infection associated with long-term down-regulation of the host's immune response. We
show here that CD4 T cell regulation is the main determinant of parasite survival. In a laboratory model of infection, using
Litomosoides sigmodontis in BALB/c mice, parasites establish for >60 days in the thoracic cavity. During infection, CD4 T cells
at this site express increasing levels of CD25, CTLA-4, and glucocorticoid-induced TNF receptor family-related gene (GITR), and
by day 60, up to 70% are CTLA-4 GITRhigh
, with a lesser fraction coexpressing CD25. Upon Ag stimulation, CD4 CTLA-
4 GITRhigh
cells are hyporesponsive for proliferation and cytokine production. To test the hypothesis that regulatory T cell
activity maintains hyporesponsiveness and prolongs infection, we treated mice with Abs to CD25 and GITR. Combined Ab
treatment was able to overcome an established infection, resulting in a 73% reduction in parasite numbers (p < 0.01). Parasite
killing was accompanied by increased Ag-specific immune responses and markedly reduced levels of CTLA-4 expression. The
action of the CD25 GITR cells was IL-10 independent as in vivo neutralization of IL-10R did not restore the ability of the
immune system to kill parasites. These data suggest that regulatory T cells act, in an IL-10-independent manner, to suppress host
immunity to filariasis. The Journal of Immunology, 2005, 174: 49244933.

  

Source: Allen, Judith - School of Biological Sciences, University of Edinburgh
Maizels, Rick - School of Biological Sciences, University of Edinburgh

 

Collections: Biology and Medicine; Environmental Sciences and Ecology