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Antigenic Mimicry: Onchocerca volvulus Antigen-Specific T Cells and Ocular Inflammation

¹ From the University of Bristol, Department of Pathology and Microbiology, School of Medical Sciences, Bristol, United Kingdom; and the ² Diabetes Research Center, Yale University School of Medicine, New Haven, Connecticut.

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 onchocerciases.

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