CD8⁺ T cells from patients with acute multiple sclerosis display selective increase of adhesiveness in brain venules: A critical role for P-selectin glycoprotein ligand-1

Multiple sclerosis (MS) is considered an autoimmune inflammatory disease of the central nervous system. Under physiologic conditions, we compared the adhesiveness of CD4⁺ and CD8⁺ lymphocytes from nontreated patients with acute, relapsing-remitting multiple sclerosis (RRMS) and from healthy donors. We show that in patients with RRMS CD8⁺, but not with RRMS CD4⁺, T cells display increased rolling and arrest in inflamed murine brain venules. Moreover, CD8⁺, but not CD4⁺, lymphocytes from MS patients show increased rolling on P-selectin in vitro. Anti-P-selectin glycoprotein ligand-1 (PSGL-1) antibodies dramatically block the recruitment of CD8⁺ cells in brain vessels of patients with MS, suggesting that PSGL-1 represents a novel pharmaceutical target that may be exploited to block the selective entrance of CD8⁺ cells during early inflammation. Vascular cell adhesion molecule-1 (VCAM-1), but not PSGL-1, is critical for the adhesion of CD4⁺ cells in MS patients, high-lighting a fundamental dichotomy in the mechanisms governing the recruitment of lymphocyte subsets in RRMS. Importantly, 7-color fluorescence-activated cell sorter (FACS) analysis, together with functional data, indicates that a large fraction of CD8⁺ cells from MS patients display the characteristics of memory-effector phenotype. In conclusion, our results show that CD8⁺, but not CD4⁺, T cells from patients with RRMS in the acute phase of the disease display increased ability to be recruited in inflamed brain venules.