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During acute graft-versus-host disease (aGVHD) in mice, autoreactive T cells can be generated de novo in the host thymus implying an impairment in self-tolerance induction. As a possible mechanism, we have previously reported that mature medullary thymic epithelial cells (mTEC(high)) expressing the autoimmune regulator are targets of donor T-cell alloimmunity during aGVHD. A decline in mTEC(high) cell pool size, which purges individual tissue-restricted peripheral self-antigens (TRA) from the total thymic ectopic TRA repertoire, weakens the platform for central tolerance induction. Here we provide evidence in a transgenic mouse system using ovalbumin (OVA) as a model surrogate TRA that the de novo production of OVA-specific CD4(+) T cells during acute GVHD is a direct consequence of impaired thymic ectopic OVA expression in mTEC(high) cells. Our data, therefore, indicate that a functional compromise of the medullary mTEC(high) compartment may link alloimmunity to the development of autoimmunity during chronic GVHD.

Original publication

DOI

10.1182/blood-2014-08-597245

Type

Journal article

Journal

Blood

Publication Date

23/04/2015

Volume

125

Pages

2720 - 2723

Keywords

Animals, Autoantigens, Autoimmunity, CD4-Positive T-Lymphocytes, Female, Graft vs Host Disease, Mice, Mice, Inbred C57BL, Mice, Transgenic, Ovalbumin, Self Tolerance, Thymus Gland