EXPERIMENTAL ONCHOCERCIASIS IN CHIMPANZEES - CELLULAR-RESPONSES AND ANTIGEN RECOGNITION AFTER IMMUNIZATION AND CHALLENGE WITH ONCHOCERCA-VOLVULUS INFECTIVE 3RD-STAGE LARVAE

Immunization of chimpanzees with radiation-attenuated infective 3rd-st age larvae (L3) of Onchocerca volvulus did not induce strong protectiv e immunity against a subsequent challenge infection; only 1 out of 4 i mmunized animals remained non-patent (i.e. microfilariae-negative) aft er challenge, and may have been protected. However, during immunizatio n and before challenge, a broad range of adult 0. volvulus-derived ant igens (OvAg) and also uterus-derived OvAg were recognized by circulati ng antibodies; moreover, the repertory of antigens recognized increase d further in subsequently patent animals after challenge, particularly in the range of M(r) 12-42 kDa. In the immunized and non-patent chimp anzee, by contrast, serological recognition of uterus-derived OvAg wit h M(r) 14 kDa and 105 kDa disappeared by 19 months post-challenge (p.c .). During immunization, Acanthocheilonema viteae L3 antigens of M(r) 11-12 kDa were strongly recognized only by the non-patent animal, sugg esting that recognition of these antigens may have supported resistanc e to the subsequent challenge infection. In immunized chimpanzees, a s ubstantial increase in the cellular reactivity to OvAg was induced; th is, however, declined by 19 months p.c. to levels similar to those see n prior to immunization. At that time, 3 out of 4 immunized animals we re patently infected. The effect of exogenous cytokines on in vitro-re activity of PBMC to OvAg was examined, Addition of exogenous IL-2 alon e, IFN-gamma alone, and IFN-gamma in combination with IL-2, did not au gment net cellular responses to OvAg by PBMC from infected and control chimpanzees. In the presence of IL-4 alone, IL-6 alone, IL-2 with IL- 4, IL-2 with IL-4 and IFN-gamma, or IL-2 with IL-4 and IL-6, the net c ellular reactivity to OvAg increased significantly in patent chimpanze es and reached levels similar to non-patent animals. Thus, non-patent chimpanzees maintain high cellular reactivity to OvAg and in vitro cel lular unresponsiveness to OvAg on the part of patent chimpanzees is re versible after addition of several cytokines which act individually or synergistically.