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 language | English |
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Pages (from-to) | 6608-6611 |
Number of pages | 4 |
Journal | Blood |
Volume | 117 |
Issue number | 24 |
DOIs | |
Publication status | Published - 2011 Jun 16 |
Externally published | Yes |
ASJC Scopus subject areas
- Biochemistry
- Immunology
- Hematology
- Cell Biology