Defective regulatory and effector T cell functions in patients with FOXP3 mutations

Rosa Bacchetta, Laura Passerini, Eleonora Gambineri, Minyue Dai, Sarah E. Allan, Lucia Perroni, Franca Dagna-Bricarelli, Claudia Sartirana, Susanne Matthes-Martin, Anita Lawitschka, Chiara Azzari, Steven F. Ziegler, Megan K. Levings, Maria Grazia Roncarolo

Research output: Contribution to journalArticlepeer-review


The autoimmune disease immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) is caused by mutations in the forkhead box protein P3 (FOXP3) gene. In the mouse model of FOXP3 deficiency, the lack of CD4 +CD25+ Tregs is responsible for lethal autoimmunity, indicating that FOXP3 is required for the differentiation of this Treg subset. We show that the number and phenotype of CD4+CD25+ T cells from IPEX patients are comparable to those of normal donors. CD4 +CD25high T cells from IPEX patients who express FOXP3 protein suppressed the in vitro proliferation of effector T cells from normal donors, when activated by "weak" TCR stimuli. In contrast, the suppressive function of CD4+CD25high T cells from IPEX patients who do not express FOXP3 protein was profoundly impaired. Importantly, CD4 +CD25high T cells from either FOXP3+ or FOXP3- IPEX patients showed altered suppression toward autologous effector T cells. Interestingly, IL-2 and IFN-γ production by PBMCs from IPEX patients was significantly decreased. These findings indicate that FOXP3 mutations in IPEX patients result in heterogeneous biological abnormalities, leading not necessarily to a lack of differentiation of CD4+CD25 high Tregs but rather to a dysfunction in these cells and in effector T cells.

Original languageEnglish
Pages (from-to)1713-1722
Number of pages10
JournalJournal of Clinical Investigation
Issue number6
Publication statusPublished - Jun 1 2006

ASJC Scopus subject areas

  • Medicine(all)


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