Uveitis induced by lymphocytes sensitized against a transgenically expressed lens protein.
OBJECTIVE
Previously established experimental models for lens-associated uveitis (LAU) are all mediated by antibodies. The present study analyzed the features of a novel experimental intraocular inflammatory eye disease that is mediated by lymphocytes targeted at a lens antigen.


METHODS
Conventional technologies were used to generate three lines of transgenic (Tg) mice, expressing hen egg lysozyme (HEL) under the control of the alphaA-crystallin promoter. To induce intraocular inflammation, these Tg mice were injected with lymphocytes from syngeneic wild-type donors sensitized against HEL. Before their injection, the cells were stimulated in culture with HEL. To release lenticular material, some eyes were capsulotomized. Ocular histopathologic changes were examined by routine methods. Levels of HEL antibody were measured by enzyme-linked immunosorbent assay, whereas cellular immunity was determined by the lymphocyte proliferation assay.


RESULTS
Intraocular inflammation developed in HEL-Tg mice injected with syngeneic lymphocytes sensitized against HEL. The severity of inflammation was directly related to the number of injected cells, as well as to the accessibility of HEL. The most intense inflammation was seen in Tg mice in which the lens was disintegrated due to high production of HEL. In mice with no apparent lenticular changes the inflammation was enhanced by capsulotomy. The inflammation affected all segments of the eye and persisted for at least 39 days after adoptive transfer of cells. Four days after cell injection, the inflammation consisted of subacute infiltration, with both mononuclear and polymorphonuclear leukocytes, whereas more chronic infiltration was seen at later times. Vigorous cellular immunity but no antibody to HEL was found in recipient mice, thus demonstrating the exclusive participation of cellular immunity in the pathogenesis of this experimental disease.


CONCLUSIONS
Transgenic mice expressing HEL in their lenses develop intraocular inflammation after injection of syngeneic lymphocytes sensitized against HEL. This experimental disease is a novel cell-mediated model for LAU.
Lai
J C
JC
National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892-1857, USA.
Lobanoff
M C
MC
Fukushima
A
A
Wawrousek
E F
EF
Chan
C C
CC
Whitcup
S M
SM
Gery
I
I
D019264:Adoptive Transfer; D000818:Animals; D000917:Antibody Formation; D003459:Crystallins / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007111:Immunity, Cellular; D007903:Lens Capsule, Crystalline / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D009113:Muramidase / Q000276:immunology; D013154:Spleen / Q000276:immunology; D014605:Uveitis / Q000209:etiology* / Q000276:immunology / Q000473:pathology
D003459:Crystallins; D009113:Muramidase