CD25 deficiency causes an immune dysregulation, polyendocrinopathy, enteropathy, X-linked-like syndrome, and defective IL-10 expression from CD4 lymphocytes

J Allergy Clin Immunol. 2007 Feb;119(2):482-7. doi: 10.1016/j.jaci.2006.10.007. Epub 2006 Dec 27.


Background: Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) results in systemic autoimmunity from birth and can be caused by mutations in the transcription factor forkhead box P3 (FOXP3).

Objective: To determine if Foxp3 is required for the generation of IL-10-expressing T regulatory cells.

Methods: CD4 lymphocytes were isolated from patients with IPEX-like syndromes and activated with antibodies to CD3 and CD46 to generate IL-10-expressing T regulatory cells.

Results: We describe a patient with clinical manifestations of IPEX that had a normal Foxp3 gene, but who had CD25 deficiency due to autosomal recessive mutations in this gene. This patient exhibited defective IL-10 expression from CD4 lymphocytes, whereas a Foxp3-deficient patient expressed normal levels of IL-10.

Conclusion: These data show that CD25 deficiency results in an IPEX-like syndrome and suggests that although Foxp3 is not required for normal IL-10 expression by human CD4 lymphocytes, CD25 expression is important.

Clinical implications: Any patient with features of IPEX but with a normal Foxp3 gene should be screened for mutations in the IL-2 receptor subunit CD25.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • CD4-Positive T-Lymphocytes / immunology*
  • Child
  • Forkhead Transcription Factors / genetics
  • Genetic Diseases, X-Linked / genetics*
  • Humans
  • Interleukin-10 / biosynthesis*
  • Interleukin-15 / pharmacology
  • Interleukin-2 / pharmacology
  • Interleukin-2 Receptor alpha Subunit / deficiency*
  • Interleukin-2 Receptor alpha Subunit / genetics
  • Intestinal Diseases / genetics*
  • Male
  • Polyendocrinopathies, Autoimmune / genetics*
  • Syndrome


  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Interleukin-15
  • Interleukin-2
  • Interleukin-2 Receptor alpha Subunit
  • Interleukin-10