Md. Carrithers et al., Differential adhesion molecule requirements for immune surveillance and inflammatory recruitment, BRAIN, 123, 2000, pp. 1092-1101
Activated CD4 Th1 lymphocytes can enter the brain in the absence of an infl
ammatory focus. However, the molecular mediators that regulate this early m
igration of lymphocytes into the brain have remained unclear. We hypothesiz
ed that the entry of these 'pioneer' lymphocytes into the brain is regulate
d by a set of molecular events that are distinct from those used once infla
mmation has been established. Using cells fluorescently labelled with the l
ipophilic dye DiI, myelin basic protein (MBP)-specific CD4 lymphocytes that
expressed low or high levels of very late antigen-4 (VLA-4) and non-antige
n-specific activated splenocytes homed to mouse brain in similar quantities
2 h after adoptive transfer. However, antigen specificity and VLA-4 expres
sion were required for more robust recruitment by 24 h, Immunocytochemistry
revealed endothelial and microenvironmental upregulation of vascular cell
adhesion molecule (VCAM), intercellular cell adhesion molecule 1 (ICAM-1),
MHC class II and interferon-gamma 48 h after transfer of MBP-specific cells
. In contrast, expression of meningeal and choroid plexus-associated P sele
ctin was upregulated 2 h after adoptive transfer, but not at 48 h, Monoclon
al antibody to P selectin, but not to VLA-4, inhibited early migration of h
igh VLA-LL-expressing MBP-specific lymphocytes. These results suggest that
early migration occurs independent of the lymphocyte integrin VLA-4 and end
othelial VCAM, but does require increased surface expression of endothelial
P selectin.