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Antigenic mimicry: Onchocerca volvulus antigen-specific T cells and ocular inflammation
Nicol M McKechnie1, Werner Gürr, Hanano Yamada
1University of Bristol, Department of Pathology and Microbiology, School of Medical Sciences, Bristol, United Kingdom. n.m.mckechnie@bris.ac.uk
Purpose:
Molecular mimicry has been suggested to play a role in the development of ocular onchocerciasis. The Onchocerca volvulus antigen Ov39 is cross-reactive with the retinal antigen hr44 and induces ocular inflammation in rats after immunization. This study was undertaken to determine whether Ov39-derived T-cell lines, which proliferate in response to stimulation with hr44, can transfer disease to naive Lewis rats.
Methods:
Two separately derived IL-2-dependent CD4(+) T-cell lines, LKOV39 1.8 and LKOV39 4.5, specific to Ov39 were transferred to naïve Lewis rats. A T-cell line specific to the peripheral nerve protein P2 served as a positive control for transfer of disease. Ocular tissues were analyzed by immunohistology, and sera were tested for the presence of antibodies to hr44.
Results:
Transfer of both T-cell lines caused inflammation of the limbus, iris, and choroid. In addition, LKOV39 1.8, which produced slightly more inflammation, induced activation of retinal microglia. LKOV39 4.5 induced a dose-dependent influx of CD8(+) cells into the limbus and the uvea. Sera from rats that received the T-cell lines had no significant antibody responses to hr44.
Conclusions:
These findings indicate that CD4(+) cell lines specific to the antigen Ov39 can induce ocular inflammation in naïve rats and suggest that recruitment of CD8(+) T cells may play a regulatory role. The inflammation is milder than that produced by immunization. The absence of antibody responses to hr44 in the animals receiving the T-cell lines may indicate a role for antibody in the development of ocular onchocerciasis.