Antigenic mimicry: Onchocerca volvulus antigen-specific T cells and ocular inflammation.
OBJECTIVE
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.
McKechnie
Nicol M
NM
University of Bristol, Department of Pathology and Microbiology, School of Medical Sciences, Bristol, United Kingdom. n.m.mckechnie@bris.ac.uk
Gürr
Werner
W
Yamada
Hanano
H
Copland
David
D
Braun
Gabriele
G
D019264:Adoptive Transfer; D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology*; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D003429:Cross Reactions / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D005136:Eye Proteins / Q000276:immunology; D007124:Immunoenzyme Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008565:Membrane Proteins / Q000276:immunology; D018716:Molecular Mimicry; D017181:Onchocerca volvulus / Q000276:immunology*; D015827:Onchocerciasis, Ocular / Q000276:immunology* / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D014605:Uveitis / Q000276:immunology* / Q000473:pathology
D000947:Antigens, Helminth; D005136:Eye Proteins; D008565:Membrane Proteins; C095845:Ov39 antigen; C095844:hr44 antigen; D018799:Intercellular Adhesion Molecule-1