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CTLA-4 and CD4 CD25 Regulatory T Cells Inhibit Protective Immunity to Filarial Parasites In Vivo1
 

Summary: CTLA-4 and CD4 CD25 Regulatory T Cells Inhibit
Protective Immunity to Filarial Parasites In Vivo1
Matthew D. Taylor,2
* Anjanette Harris, Simon A. Babayan, Odile Bain,
Abigail Culshaw,
Judith E. Allen, and Rick M. Maizels
The T cell coinhibitory receptor CTLA-4 has been implicated in the down-regulation of T cell function that is a quintessential feature
of chronic human filarial infections. In a laboratory model of filariasis, Litomosoides sigmodontis infection of susceptible BALB/c mice,
we have previously shown that susceptibility is linked both to a CD4 CD25 regulatory T (Treg) cell response, and to the development
of hyporesponsive CD4 T cells at the infection site, the pleural cavity. We now provide evidence that L. sigmodontis infection drives
the proliferation and activation of CD4 Foxp3 Treg cells in vivo, demonstrated by increased uptake of BrdU and increased expression
of CTLA-4, Foxp3, GITR, and CD25 compared with naive controls. The greatest increases in CTLA-4 expression were, however, seen
in the CD4 Foxp3 effector T cell population which contained 78% of all CD4 CTLA-4 cells in the pleural cavity. Depletion of CD25
cells from the pleural CD4 T cell population did not increase their Ag-specific proliferative response in vitro, suggesting that their
hyporesponsive phenotype is not directly mediated by CD4 CD25 Treg cells. Once infection had established, killing of adult parasites
could be enhanced by neutralization of CTLA-4 in vivo, but only if performed in combination with the depletion of CD25 Treg cells.
This work suggests that during filarial infection CTLA-4 coinhibition and CD4 CD25 Treg cells form complementary components of
immune regulation that inhibit protective immunity in vivo. The Journal of Immunology, 2007, 179: 46264634.
D
own-regulation of T cell function resulting in immune

  

Source: Allen, Judith - School of Biological Sciences, University of Edinburgh
MacDonald, Andrew - Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh
Maizels, Rick - School of Biological Sciences, University of Edinburgh

 

Collections: Biology and Medicine; Environmental Sciences and Ecology