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Peripheral autoantigen induces regulatory T cells that prevent autoimmunity
1Medical Research Council Cellular Immunology Unit, Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom. bseddon@nimr.mrc.ac.uk
The Journal of Experimental Medicine
|March 2, 1999
Summary
Regulatory T cells preventing autoimmune thyroiditis require the presence of the specific autoantigen for their generation. This highlights the crucial role of antigen in stimulating regulatory immune responses.
Area of Science:
- Immunology
- Autoimmunity
- T cell regulation
Background:
- Autoimmune thyroiditis can be induced in rats via thymectomy and irradiation.
- Disease development is preventable by reconstituting rats with specific T cell populations.
- The antigen specificity of these regulatory T cells remained unaddressed.
Purpose of the Study:
- To investigate the role of autoantigen presence in the generation of regulatory T cells that prevent autoimmune thyroiditis.
- To determine if peripheral T cells require autoantigen exposure for their regulatory function.
Main Methods:
- Induction of autoimmune thyroiditis in PVG rats.
- Adoptive transfer of CD4(+) T cells and CD4(+)CD8(-) thymocytes from normal and autoantigen-exposed donors into thymectomized and irradiated recipients.
- Utilizing 131I to ablate thyroids in utero to create autoantigen-deficient donors.
Main Results:
- Peripheral CD4(+) T cells from rats with ablated thyroids failed to prevent autoimmune thyroiditis.
- This regulatory deficit was specific to thyroid autoimmunity, as these cells could prevent diabetes.
- CD4(+)CD8(-) thymocytes from autoantigen-exposed donors retained their ability to prevent thyroiditis.
Conclusions:
- The presence of the relevant autoantigen in vivo is essential for generating peripheral regulatory T cells that suppress autoimmune thyroiditis.
- Regulatory T cell generation is stimulated by the peripheral autoantigen acting on thymic emigrant precursors.