IMMUNOREGULATION IN ONCHOCERCIASIS - PREDOMINANCE OF TH1-TYPE RESPONSIVENESS TO LOW-MOLECULAR-WEIGHT ANTIGENS OF ONCHOCERCA-VOLVULUS IN EXPOSED INDIVIDUALS WITHOUT MICROFILARIDERMIA AND CLINICAL-DISEASE

Chronic and generalized onchocerciasis is associated with suppression of the parasite-specific cellular responsiveness, while exposed indivi duals without parasitological and clinical evidence of infection (ende mic normals) display prominent cellular reactivity to Onchocerca volvu lus antigens (OvAg). In order to identify those parasite antigens whic h may account for this differential cellular responsiveness, total adu lt worm-derived OvAg were fractionated by means of preparative SDS-PAG E and blot-elution into 22 antigen fractions of continuously decreasin g molecular weight. Peripheral blood mononuclear cells (PBMC) from mic rofilariae (mf)-positive onchocerciasis patients (n = 18) proliferated weakly in response to all OvAg fractions. In contrast, in vitro react ivity of PBMC from endemic normals (n = 9) was depressed in response t o OvAg of mol. wt 200-30 kD only, while antigens of mol. wt <30 kD ind uced vigorous proliferation in these individuals compared with the mic rofilaridermic patients (P < 0.05). Highest proliferative reactivity o f cells from endemic normals was observed in response to OvAg of mol. wt 15-11 kD. Furthermore, these low mol. wt antigen fractions induced substantial production of IL-2 and interferon-gamma (IFN-gamma) in PBM C from endemic normals, but not in those from onchocerciasis patients. Cells from individuals of both groups secreted similar amounts of IL- 5 in response to all OvAg fractions, with highest production again bei ng induced by low mol. wt OvAg. In contrast, PBMC from onchocerciasis patients clearly produced more IL-10 than did cells from endemic norma ls. This augmented IL-10 production by PBMC from mf-positive individua ls was not only observed after stimulation with OvAg fractions, but wa s measured in unstimulated control cultures as well. IFN-gamma-specifi c mRNA in antigen-stimulated PBMC from endemic normals appeared to be more prominent than in cells from onchocerciasis patients. However, mR NA transcripts of IL-10 and IL-13 were clearly present in patients, bu t were absent or inconsistently observed in endemic normals. Our resul ts suggest that vigorous Th1-type cellular responsiveness encountered in endemic normals is restricted to low mol. wt antigens of O. volvulu s, while such reactivity will not be present in mf-positive individual s. Furthermore, spontaneous production of high levels of IL-10 in onch ocerciasis patients is likely to suppress Th1-type immunity, and thus may favour manifestation of chronic onchocerciasis. These traits of ce llular immunity may contribute to the differential outcome of O. volvu lus infection, the manifestation of clinical disease, and may also reg ulate the build up of acquired immunity in humans.