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.

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