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

Abstract

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.

• Authors: Amy A Caudy, Sreelatha T Reddy, Talal Chatila, John P Atkinson, James W Verbsky
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 119 Issue 2 Pg. 482-7 (Feb 2007) ISSN: 0091-6749 [Print] United States
• PMID: 17196245 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• 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, genetics)
• Intestinal Diseases (genetics)
• Male
• Polyendocrinopathies, Autoimmune (genetics)
• Syndrome