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Tolerance to class II MHC in transgenic mice
D Lo1, L C Burkly, R A Flavell
1Laboratory of Reproductive Physiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104, USA.
Seminars in Immunology
|November 1, 1989
Summary
Transgenic mice reveal new insights into T cell development and tolerance. Thymic epithelium induces tolerance differently than bone marrow cells, and peripheral tolerance may rely on clonal paralysis, not deletion.
Area of Science:
- Immunology
- Transgenic animal models
Background:
- T cell development and repertoire selection are fundamental to adaptive immunity.
- Understanding immune tolerance is crucial for preventing autoimmunity and managing transplants.
Purpose of the Study:
- To investigate the mechanisms of T cell tolerance induction using transgenic mouse models.
- To compare tolerance induction in the thymus versus the periphery.
Main Methods:
- Utilized transgenic mice with targeted I-E expression.
- Employed novel monoclonal antibodies to identify T cell receptors specific for class II I-E molecules.
- Studied T cell development and tolerance in vivo.
Main Results:
- Thymic epithelium demonstrates significant tolerance-inducing capability, distinct from clonal deletion by bone marrow-derived cells.
- Peripheral tolerance to tissue-restricted antigens appears not to be mediated by clonal deletion.
- Clonal paralysis is suggested as a key mechanism for peripheral tolerance induction and maintenance.
Conclusions:
- Thymic and peripheral tolerance mechanisms differ.
- Clonal paralysis is a significant pathway for maintaining peripheral immune tolerance.