Defective inhibition of B-cell proliferation by Wiskott-Aldrich syndrome protein-deficient regulatory T cells

Marsilio Adriani, Krysten A. Jones, Toru Uchiyama, Martha R. Kirby, Christopher Silvin, Stacie M. Anderson, Fabio Candotti

    Research output: Contribution to journalArticlepeer-review

    16 Citations (Scopus)

    Abstract

    Wiskott-Aldrich syndrome (WAS) is an inherited immunodeficiency characterized by high incidence of autoantibody-mediated autoimmune complications. Such a feature has been associated with defective suppressor activity of WAS protein-deficient, naturally occurring CD4+CD25 +Foxp3+ regulatory T cells on responder T cells. However, it remains to be established whether the altered B-cell tolerance reported in WAS patients and Was knockout (WKO) mice is secondary to abnormalities in the direct suppression of B-cell function by nTreg cells or to impaired regulation of T-helper function. Because activated nTreg cells are known to induce granzyme B-mediated B-cell killing, we decided to evaluate the regulatory capabilities of WKO nTregs on B lymphocytes. We found that preactivated WKO nTreg cells failed to effectively suppress B-cell proliferation and that such a defect was associated with reduced killing of B cells and significantly decreased degranulation of granzyme B. Altogether, these results provide additional mechanistic insights into the loss of immune tolerance in WAS.

    Original languageEnglish
    Pages (from-to)6608-6611
    Number of pages4
    JournalBlood
    Volume117
    Issue number24
    DOIs
    Publication statusPublished - 2011 Jun 16

    ASJC Scopus subject areas

    • Biochemistry
    • Immunology
    • Hematology
    • Cell Biology

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