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 383%) 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 seminnual doses ofthe 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, IL4). Despite these changes, parasite-specific IL-2 and IL4 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 volwulus-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. (J. Clin. Invest. 1991. 88:231-238.)

Decreased CD4 and increased CD8 counts with T cell activation is associated with chronic helminth infection

“…Last but not least, the marked immune activation that we have found in this chronically infected population is most probably representative of much larger African populations, and was also found in Asia as well as Central and South America [50][51][52][53][54][55][56][57][58][59][60]. Such wide immune activation may have far reaching implications.…”

Down-Regulated Lymphoproliferation Coincides with Parasite Maturation and with the Collapse of Both Gamma Interferon and Interleukin-4 Responses in a Bovine Model of Onchocerciasis

“…The down-regulation of parasite-specific IL-2, IL-4, and IFN-␥ production observed in this study is particularly informative. If such a down-regulation of cytokine production occurred with O. volvulus infections, it would explain the inability of several studies of onchocerciasis patients to detect parasite-specific IL-2, IL-4, and IFN-␥ production (8,10,29,30). A role for IL-4 production in parasitespecific proliferative responses is supported by the observation that the addition of recombinant IL-4 to antigen-stimulated PBMC cultures of O. volvulus-infected chimpanzees partially restored proliferative responses (19).…”

Chronic immune activation associated with intestinal helminth infections results in impaired signal transduction and anergy

“…observed in other populations from Ethiopia (8) and other developing countries (9)(10)(11)(12)(13). After their arrival in Israel, most Eth.…”