title: Impaired in vitro regulatory T cell function associated with Wiskott-Aldrich syndrome.
abstract: Wiskott-Aldrich syndrome (WAS) is a primary immunodeficiency characterized by the contradictory coexistence of impaired T-cell function and exaggerated T-cell-mediated pathology, including autoimmunity and eczema. WAS protein (WASp)-deficient mice are also immunodeficient and can develop autoimmune disease. Since defects in regulatory T-cells (Treg) are associated with autoimmunity, we examined the presence and function of these cells in WAS patients and WASp-deficient mice. We found that CD4(+)CD25(+)FOXP3(+) Treg cells can develop in the absence of WASp expression. However, Treg cells both from WASp-deficient mice and from four out of five WAS patients studied showed impaired in vitro suppressor function. In WASp-deficient mice, this defect could be partially rescued by pre-activation with IL-2, suggesting that inadequate cell activation may play a role in WASp-deficient Treg dysfunction. These findings may provide insights into the complex pathophysiology and paradoxical phenotypes of WAS and suggest new therapeutic modalities for autoimmunity in these patients.
authors.affiliation: Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, 49 Convent Dr., Blg. 49, Rm 3A20, Bethesda, MD 20892-4442, USA.
authors.forename: Marsilio
authors.initials: M
authors.lastname: Adriani
authors.forename: Joseph
authors.initials: J
authors.lastname: Aoki
authors.forename: Reiko
authors.initials: R
authors.lastname: Horai
authors.forename: Angela M
authors.initials: AM
authors.lastname: Thornton
authors.forename: Akihiro
authors.initials: A
authors.lastname: Konno
authors.forename: Martha
authors.initials: M
authors.lastname: Kirby
authors.forename: Stacie M
authors.initials: SM
authors.lastname: Anderson
authors.forename: Richard M
authors.initials: RM
authors.lastname: Siegel
authors.forename: Fabio
authors.initials: F
authors.lastname: Candotti
authors.forename: Pamela L
authors.initials: PL
authors.lastname: Schwartzberg
mesh_terms: D019264:Adoptive Transfer; D000328:Adult; D000818:Animals; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes; D002675:Child, Preschool; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D015375:Receptors, Interleukin-2; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014923:Wiskott-Aldrich Syndrome / Q000235:genetics* / Q000276:immunology*; D051316:Wiskott-Aldrich Syndrome Protein / Q000172:deficiency / Q000235:genetics / Q000276:immunology*
chemical_list: D051858:Forkhead Transcription Factors; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D051316:Wiskott-Aldrich Syndrome Protein