The Role of T Cells Expressing TcR Vβ13 in Autoimmune Thyroiditis Induced by Transfer of Mouse Thyroglobulin-Activated Lymphocytes: Identification of Two Common CDR3 Motifs

Previous studies have shown that induction of autoimmune diabetes by adult thymectomy and split dose irradiation of PVG.RT1u rats can be prevented by their reconstitution with peripheral CD4+CD45RC−TCR-α/β+RT6+ cells and CD4+CD8− thymocytes from normal syngeneic donors. These data provide evidence for the role of regulatory T cells in the prevention of a tissue-specific autoimmune disease but the mode of action of these cells has not been reported previously. In this study, autoimmune thyroiditis was induced in PVG.RT1c rats using a similar protocol of thymectomy and irradiation. Although a cell-mediated mechanism has been implicated in the pathogenesis of diabetes in PVG.RT1u rats, development of thyroiditis is independent of CD8+ T cells and is characterized by high titers of immunoglobulin (Ig)G1 antithyroglobulin antibodies, indicating a major humoral component in the pathogenesis of disease. As with autoimmune diabetes in PVG.RT1u rats, development of thyroiditis was prevented by the transfer of CD4+CD45RC− and CD4+CD8− thymocytes from normal donors but not by CD4+CD45RC+ peripheral T cells. We now show that transforming growth factor (TGF)-β and interleukin (IL)-4 both play essential roles in the mechanism of this protection since administration of monoclonal antibodies that block the biological activity of either of these cytokines abrogates the protective effect of the donor cells in the recipient rats. The prevention of both diabetes and thyroiditis by CD4+CD45RC− peripheral cells and CD4+CD8− thymocytes therefore does not support the view that the mechanism of regulation involves a switch from a T helper cell type 1 (Th1) to a Th2-like response, but rather relies upon a specific suppression of the autoimmune responses involving TGF-β and IL-4. The observation that the same two cytokines were implicated in the protective mechanism, whether thymocytes or peripheral cells were used to prevent autoimmunity, strongly suggests that the regulatory cells from both sources act in the same way and that the thymocytes are programmed in the periphery for their protective role. The implications of this result with respect to immunological homeostasis are discussed.

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The role of regulatory T cells in autoimmune thyroiditis

Medical Council ◽

10.21518/2079-701x-2020-21-152-159 ◽

2021 ◽

pp. 152-159

Author(s):

S. I. Zhukova ◽

I. D. Kanner ◽

T. M. Mamontova ◽

E. M. Shelomentceva ◽

M. L. Maximov

Keyword(s):

Vitamin D ◽

T Cells ◽

Autoimmune Disease ◽

Autoimmune Thyroiditis ◽

Treg Cells ◽

Immunological Tolerance ◽

Protective Function ◽

Treg Function ◽

Organ Specific

Autoimmune thyroiditis is an organ-specific autoimmune disease caused by the activation of self-reactive CD4+ T cells. Regulatory T (Treg) cells are a population of T cells that play a central role in immunological tolerance by suppressing selfreactive cells. CD4+ Tregs are divided into thymic (tTreg) and peripheral (pTreg). tTregs perform their functions through cytokine-independent mechanisms, pTregs – through IL-10, TGF-β and IL-35. Tregs perform a protective function against AIT. Studies of Treg level in AIT show different results, in most cases Treg level is increased, and their function is impaired. Treg function in AIT is affected by many factors, such as the level of thyroglobulin, vitamin D etc. Apart from the Treg level itself, the Th17/Treg ratio is also crucial in AIT. Activation of Tregs and modification of the Th17/Treg ratio can be used in AIT treatment.

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