RGD Reference Report - An autoimmune disease with multiple molecular targets abrogated by the transgenic expression of a single autoantigen in the thymus. - Rat Genome Database

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An autoimmune disease with multiple molecular targets abrogated by the transgenic expression of a single autoantigen in the thymus.

Authors: Alderuccio, F  Toh, B H  Tan, S S  Gleeson, P A  van Driel, I R 
Citation: Alderuccio F, etal., J Exp Med. 1993 Aug 1;178(2):419-26. doi: 10.1084/jem.178.2.419.
RGD ID: 14696740
Pubmed: PMID:8393475   (View Abstract at PubMed)
PMCID: PMC2191118   (View Article at PubMed Central)
DOI: DOI:10.1084/jem.178.2.419   (Journal Full-text)

Many autoimmune diseases are characterized by autoantibody reactivities to multiple cellular antigens. Autoantigens are commonly defined as targets of the autoimmune B cell response, but the role, if any, of these autoantigens in T cell-mediated autoimmune diseases is generally unknown. Murine experimental autoimmune gastritis is a CD4+ T cell-mediated organ-specific autoimmune disease induced by neonatal thymectomy of BALB/c mice. The murine disease is similar to human autoimmune gastritis and pernicious anemia, and is characterized by parietal and chief cell loss, submucosal mononuclear cell infiltrates, and autoantibodies to the alpha and beta subunits of the gastric H/K ATPase. However, the specificity of T cells that cause the disease is not known. To examine the role of the H/K ATPase in this T cell-mediated disease, transgenic mice were generated that express the beta subunit of the H/K ATPase under the control of the major histocompatibility complex class II I-Ek alpha promoter. We show that transgenic expression of the gastric H/K ATPase beta subunit specifically prevents the onset of autoimmune gastritis after neonatal thymectomy. In addition, thymocyte transfer experiments suggest that tolerance of pathogenic autoreactive T cells is induced within the thymus of the transgenic mice. We conclude that the beta subunit of the gastric H/K ATPase is a major T cell target in autoimmune gastritis and that thymic expression of a single autoantigen can abrogate an autoimmune response to multiple autoantigens.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ATP4BHumanautoimmune gastritis  ISOAtp4b (Mus musculus) RGD 
Atp4bRatautoimmune gastritis  ISOAtp4b (Mus musculus) RGD 
Atp4bMouseautoimmune gastritis  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Atp4b  (ATPase H+/K+ transporting subunit beta)

Genes (Mus musculus)
Atp4b  (ATPase, H+/K+ exchanging, beta polypeptide)

Genes (Homo sapiens)
ATP4B  (ATPase H+/K+ transporting subunit beta)


Additional Information