concanavalin-a and Onchocerciasis

Characterization of in vitro lymphocyte responsiveness was performed on selected groups of onchocerciasis patients from Sudan and Sierra Leone. These patients manifested a very broad range of clinical signs and showed widely divergent parasite infection intensities. Lymphocyte proliferative responses to soluble Onchocerca volvulus antigen (sAg) were poor in infected persons; mitogen and PPD responses were maintained in the normal range in one group of patients from southwestern Sudan, but were profoundly depressed in a group from N.E. Sudan. Proliferative responses and interferon-gamma (INF-gamma) secretion were very significantly depressed in the presence of live microfilariae of O. volvulus or secretions/excretions (S/E) from microfilariae (mf) or from female, but not male, adult parasites. Lymphocyte responses were maintained near normal when exogenous IL-2 was added to these cultures. The results indicate that O. volvulus infection and its clinical consequences are not consistently associated with systemic deficits in immune responsiveness. However, suppression of lymphocyte reactivity by mf and S/E in vitro suggests that direct parasite intervention in host cell responses could be taking place in vivo, perhaps at the local microenvironment level; mediated by effects on cytokine production.

Topics: Animals; Antigens, Helminth; Concanavalin A; Female; Humans; Immunity, Cellular; In Vitro Techniques; Interferon-gamma; Interleukin-2; Lymphocyte Activation; Male; Microfilariae; Onchocerca; Onchocerciasis; Phytohemagglutinins; Sex Factors

Cellular immune responses were tested in vitro using peripheral blood mononuclear cells from 203 individuals resident in an area of Sierra Leone where onchocerciasis is hyperendemic, and 32 individuals (Gambians) with no history of contact with Onchocerca volvulus. Mean reactivity to the mitogen, Concanavalin A, did not differ between these two groups, but responses to PPD were markedly lower in those with onchocerciasis. Proliferative responses to adult female O. volvulus antigen in the latter group were generally low although elevated reactivity was found in certain sub-groups. Higher responses were evident in infected 10-14 year olds, and there was an association between elevated reactivity to O. volvulus antigens and acute reactive dermatological signs, with individuals in the latter group also carrying higher dermal microfilarial loads. A sub-group presenting with lymphadenopathy showed the strongest associations of these three parameters. These results suggested the requirement for a threshold density of dermal microfilariae for induction of acute reactivity. The presence of immunosuppressive factors in soluble O. volvulus antigen was indicated by the ability to suppress, at low concentrations, the cellular responses to PPD of a proportion of individuals.

Topics: Adolescent; Adult; Age Factors; Animals; Antigens, Helminth; Child; Child, Preschool; Concanavalin A; Female; Gambia; Humans; Immunity, Cellular; Lymphocyte Activation; Male; Middle Aged; Onchocerca; Onchocerciasis; Retrospective Studies; Sex Factors; Sierra Leone; Skin; Tuberculin