Immunoregulation in onchocerciasis: Functional and phenotypic abnormalities of lymphocyte subsets and changes with therapy

Academic Article

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 < 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.
  • Authors

    Published In

    Digital Object Identifier (doi)

    Pubmed Id

  • 18444831
  • Author List

  • Freedman DO; Lujan-Trangay A; Steel C; Gonzalez-Peralta C; Nutman TB
  • Start Page

  • 231
  • End Page

  • 238
  • Volume

  • 88
  • Issue

  • 1