Wiskott Aldrich syndrome protein (WASP) and N-WASP are critical for T cell development.

Details

Serval ID
serval:BIB_0FDB812A5A63
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Wiskott Aldrich syndrome protein (WASP) and N-WASP are critical for T cell development.
Journal
Proceedings of the National Academy of Sciences of the United States of America
Author(s)
Cotta-de-Almeida V., Westerberg L., Maillard M.H., Onaldi D., Wachtel H., Meelu P., Chung U.I., Xavier R., Alt F.W., Snapper S.B.
ISSN
0027-8424 (Print)
ISSN-L
0027-8424
Publication state
Published
Issued date
25/09/2007
Peer-reviewed
Oui
Volume
104
Number
39
Pages
15424-15429
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Although T cell dysfunction and lymphopenia are key features of immunodeficient patients with the Wiskott-Aldrich syndrome and Wiskott-Aldrich syndrome protein (WASP)-deficient mice, T cell development appears relatively normal. We hypothesized that N-WASP, a ubiquitously expressed homologue of WASP, may serve a redundant function with WASP. To examine the unique and redundant activities of WASP and N-WASP, we generated ES cells devoid of WASP and N-WASP [double knockout (DKO)] and used the RAG-2-deficient blastocyst complementation system to generate DKO lymphocytes. Moreover, we mated WASP KO mice with mice containing a conditionally targeted N-WASP allele and used the Cre-loxP system to generate mice lacking WASP and N-WASP in T cells [conditional DKO (cDKO)]. In both systems, N-WASP-deficient cells were indistinguishable from WT cells. In contrast, T cell development in DKO and cDKO mice was markedly altered, as shown by thymic hypocellularity and reduced numbers of peripheral T cells. We found that the combined activity of WASP and N-WASP was important for CD4(-)CD8(-) double-negative (DN)-to-CD4(+)CD8(+) double-positive (DP) cell transition, and this may be partly explained by reduced cycling DN3 cells. In addition, decreased migratory responses of CD4(+)CD8(-) and CD4(-)CD8(+) single-positive (SP) cells and increased percentage of CD69(low)CD24(low) and CD62L(low) SP cells in cDKO cells imply retention of SP cells in the thymus. In summary, this study suggests that, although WASP serves a unique role for peripheral T cell function, T cell development depends on the combined activity of WASP and N-WASP.

Keywords
Animals, CD4-Positive T-Lymphocytes/metabolism, CD8-Positive T-Lymphocytes/metabolism, Cell Movement, Cell Separation, Colitis/metabolism, Cytoskeleton/metabolism, Embryonic Stem Cells/cytology, Lymphocytes/metabolism, Mice, Mice, Knockout, T-Lymphocytes/metabolism, T-Lymphocytes/pathology, Thymus Gland/metabolism, Wiskott-Aldrich Syndrome Protein/physiology, Wiskott-Aldrich Syndrome Protein, Neuronal/physiology
Pubmed
Web of science
Open Access
Yes
Create date
09/10/2017 13:41
Last modification date
20/08/2019 12:36
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