Wiskott-Aldrich syndrome protein is required for NK cell cytotoxicity and colocalizes with actin to NK cell-activating immunologic synapses

Jordan S. Orange, Narayanaswamy Ramesh, Eileen Remold-O'Donnell, Yoji Sasahara, Louise Koopman, Michael Byrne, Francisco A. Bonilla, Fred S. Rosen, Raif S. Geha, Jack L. Strominger

Research output: Contribution to journalArticlepeer-review

197 Citations (Scopus)

Abstract

The Wiskott-Aldrich syndrome (WAS) is a primary immunodeficiency disorder caused by a mutation in WAS protein (WASp) that results in defective actin polymerization. Although the function of many hematopoietic cells requires WASp, the specific expression and function of this molecule in natural killer (NK) cells is unknown. Here, we report that WAS patients have increased percentages of peripheral blood NK cells and that fresh enriched NK cells from two patients with a WASp mutation have defective cytolytic function. In normal NK cells, WASp was expressed and localized to the activating immunologic synapse (IS) with filamentous actin (F-actin). Perforin also localized to the NK cell-activating IS but at a lesser frequency than F-actin and WASp. The accumulation of F-actin and WASp at the activating IS was decreased significantly in NK cells that had been treated with the inhibitor of actin polymerization, cytochalasin D. NK cells from WAS patients lacked expression of WASp and accumulated F-actin at the activating IS infrequently. Thus, WASp has an important function in NK cells. In patients with WASp mutations, the resulting NK cell defects are likely to contribute to their disease.

Original languageEnglish
Pages (from-to)11351-11356
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number17
DOIs
Publication statusPublished - 2002 Aug 20

ASJC Scopus subject areas

  • General

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