Basic and clinical immunologyCD25 deficiency causes an immune dysregulation, polyendocrinopathy, enteropathy, X-linked–like syndrome, and defective IL-10 expression from CD4 lymphocytes
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CD4 lymphocyte isolation and activation
PBMCs were obtained using Ficoll-Paque (Amersham, Piscataway, NJ) and CD4 lymphocytes isolated with magnetic beads (Miltenyi Biotec, Auburn, Calif) under an Institutional Review Board–approved human studies protocol (Washington University, St Louis, Mo). Cells were activated with plate-bound antibodies to CD3 (OKT3, American Type Tissue Collection) and CD46 (Tra2-10) with human IL-2 or human IL-15 (eBioscience, San Diego, Calif), or with 10 ng/mL phorbol 12-myristate 13-acetate and 1 μmol/L
CD25 expression, but not Foxp3, is required for IL-10 production
To test whether Foxp3 expression was required for IL-10 production from human CD4 lymphocytes, 2 patients with syndromes consistent with IPEX were analyzed. One patient had a known FOXP3 coding sequence mutation (FOXP3–),3 and the second patient had a normal Foxp3 coding sequence (Foxp3+, described). CD4 lymphocytes were isolated and stimulated with antibodies to CD3 and CD46, or CD3 and CD28 in the presence of IL-2. As shown in Fig 1, A, the Foxp3– patient expressed levels of IL-10 comparable
Discussion
Herein we describe a patient with an IPEX-like syndrome with a normal Foxp3 gene but with a deficiency in CD25. He carries a single base pair insertion of one allele of his CD25 gene and a second allele with a substitution resulting in a stop codon. Analysis of CD25 expression from parental lymphocytes shows approximately half the amount of CD25 on the surface during T-cell activation, supporting the notion that each is heterozygous at the CD25 locus. Importantly, the proliferative defect of
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Supported by National Institutes of Health grant R01-AI37618 (J.P.A.), R01-AI065617 (T.C.), the Washington University Rheumatology Postdoctoral Training Grant (A.A.C.), the Abbott Scholar Award in Rheumatology Research (J.W.V.), and the Children's Research Institute (S.T.R., J.W.V.)
Disclosure of potential conflict of interest: J. W. Verbsky has received an Abbott Scholar Award. The rest of the authors have declared that they have no conflict of interest.