Fasciola hepatica cathepsin L suppresses sheep lymphocyte proliferation in vitro and modulates surface CD4 expression on human and ovine T cells.
Fasciola hepatica infection has been shown to suppress sheep lymphocyte proliferation in vitro and this is at least partially attributable to excretory/secretory products (ES) released by F. hepatica parasites. We identified a suppressive component in ES by analysing the effect of ES fractions, separated by gel filtration, on the proliferation of sheep T cells in vitro. A major proportion of the suppressive activity in ES was shown to coelute with the cathepsin L proteases: E64, a cysteine protease inhibitor, blocked the suppressive activity of cathepsin L. In order to identify possible mechanisms by which cathepsin L could suppress T cell proliferation, the effect of ES and F. hepatica recombinant cathepsin L (rFhCatL) on the expression of 22 different sheep T cell surface markers was analysed by flow cytometry. Incubation of sheep T cells with ES or two rFhCatL significantly reduced surface CD4 expression and this effect was prevented in the presence of E64. In similar experiments with human T lymphocytes, ES and rFhCatL were shown to down regulate surface CD4 expression. These results show that F. hepatica cathepsin L both suppresses sheep T cell proliferation and reduces surface CD4 expression on both human and ovine T cells.
Prowse
Rhoda K
RK
Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia. rhoda.prowse@med.monash.edu.au
Chaplin
Paul
P
Robinson
H Clem
HC
Spithill
Terry W
TW
D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D056668:Cathepsin L; D002403:Cathepsins / Q000235:genetics / Q000494:pharmacology*; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases; D015536:Down-Regulation; D005210:Fasciola hepatica / Q000201:enzymology / Q000472:pathogenicity*; D015801:Helminth Proteins / Q000032:analysis / Q000235:genetics / Q000494:pharmacology; D006790:Host-Parasite Interactions; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D012756:Sheep / Q000276:immunology*
D015704:CD4 Antigens; D015801:Helminth Proteins; D007166:Immunosuppressive Agents; D011994:Recombinant Proteins; D002403:Cathepsins; D003546:Cysteine Endopeptidases; C534281:CTSL protein, human; D056668:Cathepsin L