To help define the immunoregulatory defects in patients with onchocerciasis, flow cytometric analysis of circulating lymphocyte subpopulations was performed in parallel with functional assays. No significant differences in CD4/CD8 ratios were seen when microfilariae-positive individuals from Guatemala were compared with Guatemalan controls. However, the infected individuals had significantly increased numbers of circulating CD4+CD45RA+ lymphocytes (mean 38.3%) when compared with controls (mean 16.0%). Coexpression of the activation marker HLA-DR was significantly increased on CD4+ cells from infected individuals. In contrast, no up-regulation of HLA-DR was seen on CD8+ or CD19+ cells. At 1 year after initiation of treatment with semiannual doses of the microfilaricide ivermectin, there were significant increases (P less than 0.05) in the percentage of CD4+CD45RA- cells, the percentage of CD4+HLA-DR+ cells, and mitogen-induced lymphokine production (IL-2, IL-4). Despite these changes, parasite-specific IL-2 and IL-4 production which had been undetectable before treatment did not manifest itself even by the 2-yr follow-up. Defects in the T-cell activation pathway in Onchocerca volvulus-infected individuals may thus exist at several independent points; a state of parasite antigen-specific tolerance appears to remain even after the relative reversal of other generalized immunoregulatory defects.
D O Freedman, A Lujan-Trangay, C Steel, C Gonzalez-Peralta, T B Nutman
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Clinical & Experimental Immunology | 2002 |
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TW Schafer, BR Hale |
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Helminthic infections cause chronic immune activation that results in impaired signal transduction and anergy
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Identification of tgh-2, a filarial nematode homolog of Caenorhabditis elegans daf-7 and human transforming growth factor beta, expressed in microfilarial and adult stages of Brugia malayi
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Infection and immunity | 2000 |
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HN Ehigiator, AW Stadnyk, TD Lee |
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Molecular cloning and expression of Cu/Zn-containing superoxide dismutase from Fasciola hepatica
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Infection and immunity | 2000 |
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Infection and immunity | 2000 |
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Molecular cloning of a serine proteinase inhibitor from Brugia malayi
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Infection and immunity | 1995 |
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Clinical & Experimental Immunology | 1994 |
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The Journal of Cell Biology | 1994 |
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Infection and immunity | 1994 |
Parasitic Infections and the Immune System
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Parasitic Infections and the Immune System | 1994 |
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RM Locksley |
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Extracellular and cytoplasmic CuZn superoxide dismutases from Brugia lymphatic filarial nematode parasites
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J Hopkin |
Journal of the Royal College of Physicians of London | 1994 |
Evidence for an abnormal profile of interleukin-4 (IL-4), IL-5, and ?-interferon (?-IFN) in peripheral blood T cells from patients with allergic eosinophilic gastroenteritis
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Journal of Clinical Immunology | 1994 |
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Experimental onchocerciasis in chimpanzees: cellular responses and antigen recognition after immunization and challenge with Onchocerca volvulus infective third-stage larvae
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Parasitology | 1993 |
Type 2 cytokines and negative immune regulation in human infections
RL Modlin, TB Nutman |
Current Opinion in Immunology | 1993 |
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M Clerici, GM Shearer |
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Clinical & Experimental Immunology | 1992 |
Ivermectin-facilitated immunity in onchocerciasis. Reversal of lymphocytopenia, cellular anergy and deficient cytokine production after single treatment.
Soboslay PT, Dreweck CM, Hoffmann WH, Lüder CG, Heuschkel C, Görgen H, Banla M, Schulz-Key H |
Clinical & Experimental Immunology | 1992 |