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Impaired thymic expression of tissue-restricted antigens licenses the de novo generation of autoreactive CD4+ T cells in acute GVHD.
Dertschnig, Simone; Hauri-Hohl, Mathias M; Vollmer, Madeleine; Holländer, Georg A; Krenger, Werner.
Afiliación
  • Dertschnig S; Department of Biomedicine, University of Basel and Basel University Children's Hospital, Basel, Switzerland;
  • Hauri-Hohl MM; Benaroya Research Institute, Virginia Mason Hospital, Seattle, Washington;
  • Vollmer M; Department of Biomedicine, University Hospital Basel, Basel, Switzerland; and.
  • Holländer GA; Department of Biomedicine, University of Basel and Basel University Children's Hospital, Basel, Switzerland; Department of Paediatrics and the Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.
  • Krenger W; Department of Biomedicine, University Hospital Basel, Basel, Switzerland; and.
Blood ; 125(17): 2720-3, 2015 Apr 23.
Article en En | MEDLINE | ID: mdl-25691159
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.
Asunto(s)

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Timo / Linfocitos T CD4-Positivos / Autoinmunidad / Autotolerancia / Enfermedad Injerto contra Huésped Límite: Animals Idioma: En Revista: Blood Año: 2015 Tipo del documento: Article

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Timo / Linfocitos T CD4-Positivos / Autoinmunidad / Autotolerancia / Enfermedad Injerto contra Huésped Límite: Animals Idioma: En Revista: Blood Año: 2015 Tipo del documento: Article