{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T17:23:37Z","timestamp":1773422617152,"version":"3.50.1"},"reference-count":60,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2001,9,1]],"date-time":"2001-09-01T00:00:00Z","timestamp":999302400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2001,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Immune responses of individuals infected with filarial nematodes are characterized by a marked cellular hyporesponsiveness and a shift of the cytokine balance toward a Th2\/Th3 response. This modulation of cellular immune responses is considered as an important mechanism to avoid inflammatory immune responses that could eliminate the parasites. We investigated the immunomodulatory potential of a secreted cysteine protease inhibitor (onchocystatin) of the human pathogenic filaria Onchocerca volvulus. Recombinant onchocystatin (rOv17), a biologically active cysteine protease inhibitor that inhibited among others the human cysteine proteases cathepsins L and S, suppressed the polyclonally stimulated and the Ag-driven proliferation of human PBMC. Stimulated as well as unstimulated PBMC in the presence of rOv17 produced significantly more IL-10, which was paralleled in some situations by a decrease of IL-12p40 and preceded by an increase of TNF-\u03b1. At the same time, rOv17 reduced the expression of HLA-DR proteins and of the costimulatory molecule CD86 on human monocytes. Neutralization of IL-10 by specific Abs restored the expression of HLA-DR and CD86, whereas the proliferative block remained unaffected. Depletion of monocytes from the PBMC reversed the rOv17-induced cellular hyporeactivity, indicating monocytes to be the target cells of immunomodulation. Therefore, onchocystatin has the potential to contribute to a state of cellular hyporesponsiveness and is a possible pathogenicity factor essential for the persistence of O. volvulus within its human host.<\/jats:p>","DOI":"10.4049\/jimmunol.167.6.3207","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T19:30:26Z","timestamp":1398022226000},"page":"3207-3215","source":"Crossref","is-referenced-by-count":132,"title":["Modulation of Human T Cell Responses and Macrophage Functions by Onchocystatin, a Secreted Protein of the Filarial Nematode\n                    <i>Onchocerca volvulus<\/i>"],"prefix":"10.1093","volume":"167","author":[{"given":"Annett","family":"Scho\u0308nemeyer","sequence":"first","affiliation":[{"name":"Department of Molecular Parasitology, Humboldt University , Berlin ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Lucius","sequence":"additional","affiliation":[{"name":"Department of Molecular Parasitology, Humboldt University , Berlin ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bettina","family":"Sonnenburg","sequence":"additional","affiliation":[{"name":"Department of Molecular Parasitology, Humboldt University , Berlin ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norbert","family":"Brattig","sequence":"additional","affiliation":[{"name":"Institute of Medical Immunology, Charite Medical School, Humboldt University , Berlin ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Sabat","sequence":"additional","affiliation":[{"name":"Division of Clinical Chemistry, Bernhard Nocht Institute for Tropical Medicine , Hamburg ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klaus","family":"Schilling","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, University of Jena , Jena ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janette","family":"Bradley","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Salford , Manchester ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanne","family":"Hartmann","sequence":"additional","affiliation":[{"name":"Department of Molecular Parasitology, Humboldt University , Berlin ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2001,9,15]]},"reference":[{"key":"2026020208061586500_R1","first-page":"445","volume-title":"Acta Trop.","year":"1987"},{"key":"2026020208061586500_R2","first-page":"271","volume-title":"Acta Trop.","year":"1991"},{"key":"2026020208061586500_R3","first-page":"797","volume-title":"Nature","year":"1993"},{"key":"2026020208061586500_R4","first-page":"380","volume-title":"J. 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