Impaired thymic expression of tissue-restricted antigens licenses the de novo generation of autoreactive CD4+ T cells during murine acute GVHD (original) (raw)
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 medullary thymic epithelial cells expressing the autoimmune regulator (Aire(+)mTEC(high)) 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 aGVHD 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 compartment may link alloimmunity to the development of autoimmunity...
Loading Preview
Sorry, preview is currently unavailable. You can download the paper by clicking the button above.