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

Clinical signs of experimental autoimmune encephalomyelitis (EAE) are assoc iated with the selective recruitment of CD4(+) memory (CD45RB(low) CD44(hig h)) T cells into the central nervous system (CNS). However, we have found t hat 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 developmen t and ameliorated the severity of established EAE by inhibiting mononuclear cell infiltration into the CNS. Trafficking of cells into lymph nodes, how ever, a property mainly of naive cells, was essentially unaffected. In cont rast, treatment with antibody to very late activation antigen-4 (VLA-4) pre vented homing to both the CNS and to lymph nodes. This study contests previ ous 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 inflammat ion. CD44 should therefore be considered a target for immunotherapy of T-ce ll-mediated inflammatory diseases, such as multiple sclerosis.