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

Blood. 2003 Jun 15;101(12):4775-82. doi: 10.1182/blood-2002-10-3309. Epub 2003 Feb 20.

Abstract

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, highlighting 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute Disease
  • Adult
  • Antibodies / pharmacology
  • Brain / blood supply*
  • CD4-Positive T-Lymphocytes / physiology
  • CD8-Positive T-Lymphocytes / physiology*
  • Cell Adhesion*
  • Female
  • Flow Cytometry
  • Hemorheology
  • Humans
  • Male
  • Membrane Glycoproteins / immunology
  • Membrane Glycoproteins / physiology*
  • Middle Aged
  • Multiple Sclerosis / pathology*
  • P-Selectin
  • Vascular Cell Adhesion Molecule-1 / physiology
  • Venules / pathology*

Substances

  • Antibodies
  • Membrane Glycoproteins
  • P-Selectin
  • P-selectin ligand protein
  • Vascular Cell Adhesion Molecule-1