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Isolation and Th17 Differentiation of Naïve CD4 T Lymphocytes
Published on: September 27, 2013
Immunoregulation in onchocerciasis. Functional and phenotypic abnormalities of lymphocyte subsets and changes with
D O Freedman1, A Lujan-Trangay, C Steel
1Clinical Parasitology Section, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892.
Insights
Onchocerciasis infection alters immune cell populations, specifically increasing activated CD4+ T cells. Ivermectin treatment partially reverses these defects, but parasite-specific immune tolerance persists.
Area of Science:
- Immunology
- Parasitology
- Tropical Medicine
Background:
- Onchocerciasis, caused by Onchocerca volvulus, is a neglected tropical disease associated with significant immunoregulatory defects.
- Understanding these immune alterations is crucial for developing effective treatment and management strategies.
Purpose of the Study:
- To define the immunoregulatory defects in patients with onchocerciasis.
- To assess the impact of ivermectin treatment on these immune defects.
Main Methods:
- Flow cytometry was used to analyze circulating lymphocyte subpopulations (CD4+, CD8+, CD19+ cells) and activation markers (HLA-DR).
- Functional assays measured mitogen- and parasite antigen-induced lymphokine production (IL-2, IL-4).
- Analyses were conducted on microfilariae-positive individuals and controls, with follow-up after ivermectin treatment.
Main Results:
- Onchocerciasis patients showed increased CD4+CD45RA+ lymphocytes and HLA-DR coexpression on CD4+ cells compared to controls.
- Ivermectin treatment led to increased CD4+CD45RA- cells, CD4+HLA-DR+ cells, and general lymphokine production.
- Parasite-specific IL-2 and IL-4 production remained undetectable even after 2 years of treatment.
Conclusions:
- Onchocerciasis is associated with distinct immunoregulatory defects, including increased activated CD4+ T cells.
- Ivermectin treatment partially restores immune function but does not overcome parasite antigen-specific tolerance.
- Immune defects in onchocerciasis may involve multiple points in the T-cell activation pathway, leading to persistent tolerance.
Abstract:
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.
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