Suppressive antigen-presenting cells in Helminth infection.
Infection with filarial nematodes is commonly associated with a failure of T cells to proliferate in response to parasite antigen. We have investigated the possibility that antigen-presenting cells recruited during filarial infection are responsible for impairment of T cell function. We have found that the human filarial parasite Brugia malayi, when implanted into the peritoneal cavity of mice, recruits a population of adherent cells that actively block the proliferation of T cells. Phenotypic analysis of the recruited cells reveals large numbers of both macrophages and eosinophils and cell sorting experiments demonstrate that these antiproliferative cells are Mac-1-positive. Studies in gene-deficient mice have demonstrated that proliferative suppression is dependent on the in vivo production of IL-4 but not IL-5 or IL-10, while suppression in vitro is not mediated by any known antiproliferative factor. Our results suggest that helminth infection can lead to the development and/or recruitment of an IL-4-dependent macrophage population that mediates suppression via a novel mechanism.
MacDonald
A S
AS
Institute of Cell, Animal and Population Biology, University of Edinburgh, UK.
Loke
P
P
Allen
J E
JE
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology*; D001202:Ascitic Fluid / Q000166:cytology; D017178:Brugia malayi / Q000276:immunology*; D002469:Cell Separation; D018920:Coculture Techniques; D004804:Eosinophils / Q000276:immunology*; D005260:Female; D005368:Filariasis / Q000276:immunology*; D016130:Immunophenotyping; D015847:Interleukin-4 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010529:Peritoneal Cavity / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015847:Interleukin-4