Related Experiment Videos
Immunotolerance against a foreign antigen transgenically expressed in the lens
J C Lai1, A Fukushima, E F Wawrousek
1National Eye Institute, National Institutes of Health, and the Howard Hughes Medical Institute-NIH Research Scholars Program, Bethesda, Maryland 20892-1857, USA.
Investigative Ophthalmology & Visual Science
|October 7, 1998
Summary
Transgenic mice expressing hen egg lysozyme (HEL) in their eyes developed immunotolerance, primarily mediated by the thymus, not the eyes themselves. This suggests a central tolerance mechanism for self-antigens like lens crystallins.
Area of Science:
- Immunology
- Ophthalmology
- Genetics
Background:
- Understanding immunotolerance is crucial for autoimmune diseases.
- Lens crystallins are potential autoantigens.
- Transgenic models offer insights into immune privilege.
Purpose of the Study:
- To investigate immunotolerance to foreign antigens expressed in the eye.
- To determine the role of the eye versus the thymus in inducing tolerance.
- To explore mechanisms underlying tolerance to autologous lens crystallins.
Main Methods:
- Generated transgenic mice expressing hen egg lysozyme (HEL) in the lens.
- Assessed HEL presence using PCFIA and RT-PCR.
- Evaluated immune responses (cellular and humoral) after HEL immunization.
- Analyzed lymphocyte proliferation, cytokine production, and antibody levels.
Main Results:
- Transgenic mice exhibited tolerance to HEL.
- Ocular dystrophy observed in high-copy membrane-bound HEL mice.
- Tolerance persisted for months, even after eye removal.
- HEL was detected in the eyes, but not serum; HEL mRNA found in the thymus.
Conclusions:
- Central tolerance, mediated by thymic HEL expression, is the primary mechanism.
- Peripheral tolerance in the eye plays a minimal role.
- A similar central tolerance mechanism likely governs immunotolerance to lens crystallins.