Adhesion molecule expression on cerebrospinal fluid T lymphocytes: Evidence for common recruitment mechanisms in multiple sclerosis, aseptic meningitis, and normal controls

Abstract

The expression of T-cell surface antigens was investigated in the cerebrospinal fluid (CSF) and peripheral blood of 11 patients with multiple sclerosis, 6 patients with aseptic meningitis, and 16 healthy subjects. A panel of monoclonal antibodies to adhesion and activation proteins was used in combination with an anti-CD3 antibody in dual-color flow cytometry. The problem of low cell numbers in the CSF from normal individuals was overcome by use of a modified staining procedure in microtiter plates, enabling analysis of as few as 5,000 cells. The majority of T cells in the CSF of the three patient groups exhibited the phenotype of memory cells (CD45RO+). CSF T cells also expressed significantly higher levels of several adhesion and activation molecules, including very late activation (VLA) antigens 3 through 6, lymphocyte function-associated (LFA) antigen 1, LFA-3, CD2, CD26, and CD44. Comparison between the different categories revealed that peripheral blood T cells from patients with multiple sclerosis expressed significantly lower amounts of the VLA integrins 4 and 5 as well as their common beta subunit CD29, compared with normal control subjects. No differences between patients with multiple sclerosis and control subjects could, however, be seen regarding the distribution of memory/naive cells or CD4+/CD8+ cells in peripheral blood. Our data support a hypothesis that memory T cells with a high expression of several adhesion molecules are selectively recruited to the central nervous system compartment, under both pathological and normal conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Enhanced binding of lymphocytes from patients with multiple sclerosis to tumour necrosis factor-alpha (TNF-α)-treated endothelial monolayers: associations with clinical relapse and adhesion molecule expression

“…Contrary to our finding is a report describing a lower prevalence of VLA-4-bearing lymphocytes in the blood of MS patients compared with normal control subjects [29]. However, this earlier study only monitored lymphocytes with a high expression of VLA-4 obtained from patients with benign relapsing-remitting MS (EDSS range 0-2 .…”

Human cerebrospinal fluid central memory CD4+T cells: Evidence for trafficking through choroid plexus and meninges via P-selectin

“…ICAM-1 is expressed on resting endothelium in various tissues including parenchymal vessels in noninflamed human brain (18,31). ICAM-1 mediates firm arrest of circulating T cells through binding of lymphocyte function-associated antigen 1 (integrin ␣ L ␤ 2 ), which is expressed by a majority of CSF T cells from both healthy volunteers and patients with CNS inflammation, and on virtually all CNS-infiltrating leukocytes in inflammatory multiple sclerosis lesions (18,32,33). ICAM-1 was constitutively expressed in the choroid plexus of healthy mice and mediated binding of lymphocytes in vitro with a StamperWoodroof assay (34,35).…”

Flow cytometric characterization of cerebrospinal fluid cells

“…Because CSF of healthy controls is usually not available due to ethical considerations (36), patients with noninflammatory neurological disorders (NIND controls) are often included instead (37). However, Svenningsson et al (38,39) did study normal CSF by assessing the percentages of lymphocyte subsets in CSF of 34 healthy individuals, after informed consent, with 2-or 3-color flow cytometry. In addition, we studied both absolute numbers and percentages of leukocyte, lymphocyte, T lymphocyte, and dendritic cell subsets by six-color flow cytometry in 84 individuals without neurological disease undergoing spinal anesthesia (Table 1; 40).…”

“…In addition, we studied both absolute numbers and percentages of leukocyte, lymphocyte, T lymphocyte, and dendritic cell subsets by six-color flow cytometry in 84 individuals without neurological disease undergoing spinal anesthesia (Table 1; 40). The two published studies (38,39), as well as our data (40), showed that normal CSF is predominantly composed of CD4 þ T lymphocytes, mostly with a central memory phenotype, and in addition contains very low frequencies of B lymphocytes, NK cells, and NKT lymphocytes (Table 1). Dendritic cells, both myeloid as well as plasmacytoid, were also present in normal CSF, although in very low frequencies (Table 1;40,41).…”