Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P14784 (IL-2 receptor)
 3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Congenital immune deficiency states have often been valuable experimental models of nature that have significantly enhanced our understanding of the immune response. The relationship between CD4+, CD25+ and Treg cells in the induction of autoimmunity has attracted significant attention. We report herein a male child of consanguineous parents who developed at six months recurrent infections, and at age 5 years, liver dysfunction with serological expression of primary biliary cirrhosis (PBC), an autoimmune liver disease that usually affects middle-aged women. Histologically, there was intense mononuclear cell lymphoid infiltration of the intrahepatic portal tracts, CD3+CD4+T cell lymphopenia in blood and serum antibody to PDC-E2. Peripheral blood lymphocytes were completely deficient of the alpha subunit of the IL-2 receptor (IL-2Ralpha, CD 25), a marker for regulatory T cells (Tregs). Allogenic stem cell transplantation led to full recovery. This case illustrates the role of deficiency of CD4+CD25+ Treg cells in causing autoimmunity, and speaks to the potential use of allogenic stem cell transplantation for immunoreconstitution in adult PBC.
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PMID:IL-2 receptor alpha deficiency and features of primary biliary cirrhosis. 1690 70

Recently, we identified a child born with a genetic deficiency of IL-2 receptor alpha (IL-2Ralpha, CD25) expression who had several clinical manifestations of primary biliary cirrhosis (PBC). In addition, there has been suggestive evidence in both patients with PBC and their first-degree relatives that a deficiency of regulatory T cells (Tregs) is an integral component for susceptibility to PBC. Based on these observations, we generated IL-2Ralpha/CD25 deficient (IL-2Ralpha(-/-)) mice and wild-type littermate controls and followed them longitudinally for the natural history of liver immunopathology and appearance of antimitochondrial antibodies (AMAs). The analyses included immunohistochemical staining of liver and portal tract infiltrates as well as FACS profiles of lymphoid subpopulations in liver and spleen. In addition, serum cytokine profiles were quantitated. Importantly, IL-2Ralpha(-/-), but not littermate controls, develop portal inflammation and biliary ductular damage similar to human patients with PBC. CD4(+) and CD8(+) T cells predominate among portal cell infiltrates and sera reflect a Th1 cytokine bias with increased levels of IFN-gamma, TNF-alpha, IL-2 and IL-12p40. Of importance is the finding that the IL-2Ralpha(-/-) mice not only develop significantly increased serum levels of IgG and IgA, but they also develop AMAs with specificity for PDC-E2, which maps to the inner lipoyl domain of the autoantigen, all characteristics which are hallmarks of human PBC. In conclusion, the IL-2Ralpha(-/-) mice should facilitate studies of the early events in PBC and especially the tantalizing connection between Treg deficiency and autoimmunity specifically directed to mitochondrially located PDC-E2 and subsequent biliary ductular cell damage.
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PMID:IL-2 receptor alpha(-/-) mice and the development of primary biliary cirrhosis. 1705 61