title: Immunoregulation in onchocerciasis. Functional and phenotypic abnormalities of lymphocyte subsets and changes with therapy.
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.
authors.affiliation: Clinical Parasitology Section, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892.
authors.forename: D O
authors.initials: DO
authors.lastname: Freedman
authors.forename: A
authors.initials: A
authors.lastname: Lujan-Trangay
authors.forename: C
authors.initials: C
authors.lastname: Steel
authors.forename: C
authors.initials: C
authors.lastname: Gonzalez-Peralta
authors.forename: T B
authors.initials: TB
authors.lastname: Nutman
mesh_terms: D000293:Adolescent; D000328:Adult; D000943:Antigens, Differentiation / Q000032:analysis; D015704:CD4 Antigens / Q000032:analysis; D006684:HLA-DR Antigens / Q000032:analysis; D006649:Histocompatibility Antigens / Q000032:analysis; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D017493:Leukocyte Common Antigens; D016131:Lymphocyte Subsets / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009855:Onchocerciasis / Q000276:immunology* / Q000628:therapy; D010641:Phenotype
chemical_list: D000943:Antigens, Differentiation; D015704:CD4 Antigens; D006684:HLA-DR Antigens; D006649:Histocompatibility Antigens; D007376:Interleukin-2; D015847:Interleukin-4; D017493:Leukocyte Common Antigens