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Experimental onchocerciasis in chimpanzees: cellular responses and antigen recognition after immunization and challenge with Onchocerca volvulus infective third-stage larvae

Published online by Cambridge University Press:  06 April 2009

C. G. K. Lüder
Affiliation:
Institute of Tropical Medicine, University of Tübingen, Wilhelmstrasse 27, D-7400 Tübingen, Germany
P. T. Soboslay
Affiliation:
Institute of Tropical Medicine, University of Tübingen, Wilhelmstrasse 27, D-7400 Tübingen, Germany
A. M. Prince
Affiliation:
The Lindsley F. Kimball Research Institute of The New York Blood Center, New York, NY 10021, USA
B. M. Greene
Affiliation:
Division of Geographic Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
R. Lucius
Affiliation:
Institute of Parasitology, University of Hohenheim, Emil-Wolff-Strasse 34, D-7000 Stuttgart 70, Germany
H. Schulz-Key
Affiliation:
Institute of Tropical Medicine, University of Tübingen, Wilhelmstrasse 27, D-7400 Tübingen, Germany

Summary

Immunization of chimpanzees with radiation-attenuated infective 3rd-stage larvae (L3) of Onchocerca volvulus did not induce strong protective immunity against a subsequent challenge infection; only 1 out of 4 immunized animals remained non-patent (i.e. microfilariae-negative) after challenge, and may have been protected. However, during immunization and before challenge, a broad range of adult O. volvulus-derived antigens (OvAg) and also uterus-derived OvAg were recognized by circulating antibodies; moreover, the repertory of antigens recognized increased further in subsequently patent animals after challenge, particularly in the range of Mr 12–42 kDa. In the immunized and non-patent chimpanzee, by contrast, serological recognition of uterus-derived OvAg with Mr 14 kDa and 105 kDa disappeared by 19 months post-challenge (p.c.). During immunization, Acanthocheilonema viteae L3 antigens of Mr 11–12 kDa were strongly recognized only by the non-patent animal, suggesting that recognition of these antigens may have supported resistance to the subsequent challenge infection. In immunized chimpanzees, a substantial increase in the cellular reactivity to OvAg was induced; this, however, declined by 19 months p.c. to levels similar to those seen prior to immunization. At that time, 3 out of 4 immunized animals were patently infected. The effect of exogenous cytokines on in vitro-reactivity of PBMC to OvAg was examined. Addition of exogenous IL-2 alone, IFN-γ alone, and IFN-γ in combination with IL-2, did not augment 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-γ, or IL-2 with IL-4 and IL-6, the net cellular reactivity to OvAg increased significantly in patent chimpanzees and reached levels similar to non-patent animals. Thus, non-patent chimpanzees maintain high cellular reactivity to OvAg and in vitro cellular unresponsiveness to OvAg on the part of patent chimpanzees is reversible after addition of several cytokines which act individually or synergistically.

Type
Research Article
Copyright
Copyright © Cambridge University Press 1993

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