Investigative ophthalmology & visual science · 2002
Antigenic mimicry: Onchocerca volvulus antigen-specific T cells and ocular inflammation.
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McKechnie Nicol M, Gürr Werner, Yamada Hanano, Copland David, Braun Gabriele
Аннотация
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.
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.
Предметные рубрики MeSH
Adoptive TransferAnimalsAntigens, HelminthBlotting, WesternCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell LineCross ReactionsEnzyme-Linked Immunosorbent AssayEpitope MappingEye ProteinsImmunoenzyme TechniquesIntercellular Adhesion Molecule-1Lymphocyte ActivationMaleMembrane ProteinsMolecular MimicryOnchocerca volvulusOnchocerciasis, OcularRatsRats, Inbred LewUveitis