Critical requirement for the Wiskott-Aldrich syndrome protein in Th2 effector function

Blood. 2010 Apr 29;115(17):3498-507. doi: 10.1182/blood-2009-07-235754. Epub 2009 Dec 23.


Patients with Wiskott-Aldrich syndrome (WAS) have numerous immune cell deficiencies, but it remains unclear how abnormalities in individual cell types contribute to the pathologies of WAS. In T cells, the WAS protein (WASp) regulates actin polymerization and transcription, and plays a role in the dynamics of the immunologic synapse. To examine how these events influence CD4 function, we isolated the WASp deficiency to CD4(+) T cells by adoptive transfer into wild-type mice to study T-cell priming and effector function. WAS(-/-) CD4(+) T cells mediated protective T-helper 1 (Th1) responses to Leishmania major in vivo, but were unable to support Th2 immunity to Nippostrongylus brasiliensis or L major. Mechanistically, WASp was not required for Th2 programming but was required for Th2 effector function. WAS(-/-) CD4(+) T cells up-regulated IL-4 and GATA3 mRNA and secreted IL-4 protein during Th2 differentiation. In contrast, cytokine transcription was uncoupled from protein production in WAS(-/-) Th2-primed effectors. WAS(-/-) Th2s failed to produce IL-4 protein on restimulation despite elevated IL-4/GATA3 mRNA. Moreover, dominant-negative WASp expression in WT effector T cells blocked IL-4 production, but had no effect on IFNgamma. Thus WASp plays a selective, posttranscriptional role in Th2 effector function.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • GATA3 Transcription Factor / biosynthesis
  • GATA3 Transcription Factor / genetics
  • GATA3 Transcription Factor / immunology
  • Humans
  • Interferon-gamma / genetics
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Interleukin-4 / biosynthesis
  • Interleukin-4 / genetics
  • Interleukin-4 / immunology
  • Leishmania major / immunology
  • Leishmaniasis, Cutaneous / genetics
  • Leishmaniasis, Cutaneous / immunology
  • Leishmaniasis, Cutaneous / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Nippostrongylus / immunology
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • RNA, Messenger / immunology
  • Strongylida Infections / genetics
  • Strongylida Infections / immunology
  • Strongylida Infections / metabolism
  • Th1 Cells / immunology
  • Th2 Cells / immunology*
  • Th2 Cells / metabolism
  • Transcription, Genetic / genetics
  • Transcription, Genetic / immunology
  • Up-Regulation / genetics
  • Up-Regulation / immunology
  • Wiskott-Aldrich Syndrome / genetics
  • Wiskott-Aldrich Syndrome / immunology
  • Wiskott-Aldrich Syndrome / metabolism
  • Wiskott-Aldrich Syndrome Protein / genetics
  • Wiskott-Aldrich Syndrome Protein / immunology*
  • Wiskott-Aldrich Syndrome Protein / metabolism


  • GATA3 Transcription Factor
  • Gata3 protein, mouse
  • RNA, Messenger
  • Was protein, mouse
  • Wiskott-Aldrich Syndrome Protein
  • Interleukin-4
  • Interferon-gamma