CD44 is involved in selective leucocyte extravasation during inflammatory central nervous system disease.
Clinical signs of experimental autoimmune encephalomyelitis (EAE) are associated with the selective recruitment of CD4+ memory (CD45RBlow CD44high) T cells into the central nervous system (CNS). However, we have found that many of these recently recruited memory cells are CD44low, 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 naïve 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.
Brennan
F R
FR
Rheumatic Diseases Unit, Western General Hospital, Edinburgh, UK.
O'Neill
J K
JK
Allen
S J
SJ
Butter
C
C
Nuki
G
G
Baker
D
D
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D002490:Central Nervous System / Q000276:immunology; D002908:Chronic Disease; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000628:therapy*; D018960:Hyaluronan Receptors / Q000276:immunology*; D007156:Immunologic Memory; D039041:Integrin alpha4beta1; D016023:Integrins / Q000276:immunology; D007962:Leukocytes / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016201:Receptors, Lymphocyte Homing / Q000276:immunology; D055502:Secondary Prevention; D018709:Statistics, Nonparametric
D000911:Antibodies, Monoclonal; D018960:Hyaluronan Receptors; D039041:Integrin alpha4beta1; D016023:Integrins; D016201:Receptors, Lymphocyte Homing