CD44 is involved in selective leucocyte extravasation during inflammatory central nervous system disease

Brennan, F. R., O'Neill, J. K., Allen, S. J. , Butter, C., Nuki, G. and Baker, D. (1999) CD44 is involved in selective leucocyte extravasation during inflammatory central nervous system disease. Immunology, 98 (3). pp. 427-435. ISSN 0019-2805

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Item Type:Article
Item Status:Live Archive


Clinical signs of experimental autoimmune encephalomyelitis (EAE) are associated with the selective recruitment of CD4+ memory (CD45RB(low) CD44(high)) T cells into the central nervous system (CNS). However, we have found that many of these recently recruited memory cells are CD44(low), suggesting that the CD44 antigen may be involved in, and transiently lost during, the extravasation process. Indeed, administration of a CD44-specific antibody (IM7.8.1) induced leucocyte CD44 shedding and both prevented the development and ameliorated the severity of established EAE by inhibiting mononuclear cell infiltration into the CNS. Trafficking of cells into lymph nodes, however, a property mainly of naive cells, was essentially unaffected. In contrast, treatment with antibody to very late activation antigen-4 (VLA-4) prevented homing to both the CNS and to lymph nodes. This study contests previous reports that dismissed a role for CD44 in inflammation of the CNS and, coupled with observations in murine dermatitis and arthritis, suggests that CD44 is involved in the homing of primed lymphocytes to sites of inflammation. CD44 should therefore be considered a target for immunotherapy of T-cell-mediated inflammatory diseases, such as multiple sclerosis.

Keywords:beta1 integrin, Hermes antigen, allergic encephalomyelitis, animal cell, animal experiment, animal model, antigen expression, article, controlled study, immunopathogenesis, lymphocyte migration, male, memory cell, mouse, nonhuman, priority journal, signal transduction, Animals, Antibodies, Monoclonal, Antigens, CD44, CD4-Positive T-Lymphocytes, Cell Movement, Central Nervous System, Chronic Disease, Encephalomyelitis, Autoimmune, Experimental, Immunologic Memory, Integrin alpha4beta1, Integrins, Leukocytes, Lymph Nodes, Mice, Mice, Inbred BALB C, Receptors, Lymphocyte Homing, Recurrence, Statistics, Nonparametric
Subjects:C Biological Sciences > C700 Molecular Biology, Biophysics and Biochemistry
Divisions:College of Science > School of Life Sciences
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ID Code:19867
Deposited On:31 Dec 2015 21:32

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