CD44v7 interferes with activation-induced cell death by up-regulation of anti-apoptotic gene expression

Blockade of CD44v7 was described to cure trinitrobenzene sulfonic acid‐induced colitis, a disease not developed by mice with targeted deletion of the CD44v7 exon. There was evidence for a reduction in activation‐induced cell death on lamina propria lymphocytes of control as compared with CD44v7‐defi...

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Bibliographic Details
Published in:Journal of leukocyte biology 2003-07, Vol.74 (1), p.135-148
Main Authors: Marhaba, Rachid, Bourouba, Mehdi, Zöller, Margot
Format: Article
Language:English
Subjects:
adhesion molecules
Animals
apoptosis
Apoptosis - genetics
autoimmunity
bcl-X Protein
Cytoskeletal Proteins - metabolism
DNA-Binding Proteins - biosynthesis
DNA-Binding Proteins - genetics
Hyaluronan Receptors - analysis
Hyaluronan Receptors - physiology
Lymphocyte Activation
Membrane Microdomains
Mice
Mice, Transgenic
Proto-Oncogene Proteins c-bcl-2 - biosynthesis
Proto-Oncogene Proteins c-bcl-2 - genetics
Replication Protein C
rodent
signal transduction
T-Lymphocytes - metabolism
Up-Regulation
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Summary:Blockade of CD44v7 was described to cure trinitrobenzene sulfonic acid‐induced colitis, a disease not developed by mice with targeted deletion of the CD44v7 exon. There was evidence for a reduction in activation‐induced cell death on lamina propria lymphocytes of control as compared with CD44v7‐deficient mice. To elucidate the mechanism underlying the relative apoptosis resistance of CD44v7‐competent as compared with CD44v7‐deficient lymphocytes, T cell activation and induction of apoptosis were analyzed on mesenteric lymph node cells and Peyer’s patch lymphocytes of CD44v7‐deficient and CD44v4‐v7‐transgenic mice, which overexpress rat CD44v4‐v7 on T lymphocytes. CD44v7 deficiency was characterized by an increase in the percentage of apoptotic cells after stimulation, increased numbers of CD95L‐ and CD152‐positive cells, low levels of the anti‐apoptotic proteins Bcl‐2 and Bcl‐Xl, and decreased phosphorylation of the pro‐apoptotic protein BAD. Also, lymphocytes from CD44v4‐v7‐transgenic mice displayed reduced levels of CD95L, low numbers of apoptotic cells, and constitutively elevated levels of Bcl‐Xl. When stimulating lymphocytes by CD3 cross‐linking, CD44v7 was not recruited toward the immunological synapse and preferentially associated with the cytoskeletal‐linker protein ezrin. Thus, as opposed to the CD44 standard isoform, CD44v7 does not function as an accessory molecule; instead, it supports survival of activated T cells by interfering with activation‐induced cell death.
ISSN:0741-5400
1938-3673
DOI:10.1189/jlb.1202615