Enhanced endothelial cell adhesion of human cerebrospinal fluid lymphocytes

Lymphocyte migration into a tissue depends on properties of both the lymphocyte and the tissue's vascular endothelium. The central nervous system (CNS) possesses a specialized microvasculature and lymphocytes appear to enter the CNS less readily than peripheral tissues. We investigated whether those lymphocytes that interact with the CNS, as represented by cerebrospinal fluid (CSF)-derived lymphocytes, express adhesive properties distinct from peripheral blood lymphocytes (PBLs). Adhesion of human lymphocytes to bovine endothelial cell monolayers was quantitated microscopically. A greater number of PBLs adhered to aortic than to retinal endothelial cell cultures (e.g., 10.9 +/- 0.6 and 4.5 +/- 0.2, respectively; p = 0.0023). Preincubation of either endothelial cell type with tumor necrosis factor-alpha (TNF-alpha) enhanced lymphocyte adhesion. Activation of PBLs with concanavalin A or phytohemagglutinin increased endothelial cell adhesion and the effect was additive with that of TNF-alpha. The number of CSF lymphocytes adhering to endothelial cell cultures (retinal, 67.5 +/- 9.0; aortic, 83.7 +/- 10.6) was more than 10 times the number of PBLs (retinal, 5.4 +/- 0.8; aortic, 8.0 +/- 1.3; p < 0.0001). CSF lymphocytes did not, however, adhere preferentially to CNS-derived endothelial cell cultures. These results suggest that CSF may be enriched, compared with peripheral blood, in its content of surveillance lymphocytes, but that these cells might enter target tissues nonspecifically.