Cerebrospinal Fluid Lymphocyte Subpopulations Research Articles

Main lymphocyte subpopulations in cerebrospinal fluid and peripheral blood in HIV-1 subtypes C and B.

HIV-1 subtype C (HIV-1C) shows reduced Tat protein chemoattractant activity compared with HIV-1B. The impact of HIV-1C Tat on the chemotaxis of the main lymphocyte subpopulations in the cerebrospinal fluid (CSF) and the peripheral blood (PB) is unclear. We hypothesized that there would be a lower frequency of specific lymphocyte subpopulations CD3+ or CD19+ in CSF in HIV-1C than in HIV-1B. The objectives were to detect the differences in the proportions of main lymphocyte subpopulations in CSF and PB, between people with HIV (PWH) and HIV-1-uninfected volunteers (PWoH) and in HIV-1B and HIV-1C. Lymphocyte immunophenotyping was studied in CSF and paired PB samples of PWH (n = 22) and PWoH (n = 14). Lymphocytes were analyzed within the CD45+ gated region. The proportions of CSF CD3+CD4+, CD3+CD8+, and CD3-CD19+ lymphocytes in CSF were comparable in HIV-1B and C. There was an increase in the proportion of CD3+CD8+ cells and a decrease in CD3+CD4+ T cells (ps = 0.016) in the CSF samples of the PWH compared with the PWoH group. In the PWH group, both CD3+CD4+ and CD3+CD8+ lymphocytes were significantly higher in the CSF than in the PB (p = 0.047 and 0.005). The proportion of CD3+CD4+ was lower and that of CD3+CD8+ was higher in the CSF samples of the aviremic group than that of HIV-negative control (p = 0.0008 and < 0.0001, respectively). HIV-1C Tat substitution (C30S) did not interfere with the CNS migration of the main lymphocyte subpopulations. This is the first study to evaluate these lymphocytes in CSF and PB of HIV-1C compared with HIV-1B.

Cerebrospinal fluid immunological biomarkers associated with axonal damage in multiple sclerosis.

Cerebrospinal fluid (CSF) neurofilament light protein (NFL) is a promising biomarker of axonal injury and neurodegeneration. Here CSF lymphocyte subpopulations and antibodies, potential players of neurodegeneration, are examined in relation to CSF NFL shedding in MS. Cerebrospinal fluid NFL from 127 consecutive untreated MS patients was analysed. Samples from 37 age-matched patients with other central nervous system non-inflammatory neurological diseases (NIND) were also assessed. CD4+, CD8+, CD56+ and CD19+ cell subsets were studied by flow cytometry. Oligoclonal IgG and IgM bands (OCMB) against lipids were studied by isoelectric focusing and immunoblotting. These data were analysed in relation to clinical and magnetic resonance imaging features. A CSF NFL cut-off value of 900ng/l (mean+3 SD of NIND values) was calculated. MS patients with increased NFL values showed significantly higher Multiple Sclerosis Severity Score and magnetic resonance imaging lesion number. The presence of OCMB (P<0.0001) and elevated T and B lymphocyte counts was associated with increased levels of CSF NFL. High CSF NFL levels are associated with elevated CSF lymphocyte cell counts and intrathecal synthesis of IgM against lipids. These findings support a role for OCMB in the axonal damage of MS offering a rationale for the association of these antibodies with disability and brain atrophy progression in MS.

Cerebrospinal fluid lymphocyte subpopulations before and after pneumoencephalography.

Pneumoencephalography (PEG) did not cause significant changes in cerebrospinal fluid (CSF) lymphocyte subpopulations. Sheep erythrocyte rosette-forming cells (E-RFC) percentage was higher in CSF before (84.0) and after (81.1) PEG than in blood (63.7). The percentage of complement receptor bearing cells was significantly higher in CSF (65.3 and 64.6) than in blood (33.1). Fcgamma receptor bearing cell levels were only slightly higher in CSF (35.6%) than in blood (31.5%), and increased after PEG to 43.9%. The high percentages of both E-RFC and complement receptor bearing cells in CSF, suggest that a considerable number of these cells bear both receptors, in contrast to blood.

Lymphocyte subpopulations in cerebrospinal fluid and peripheral blood in multiple sclerosis.

Lymphocytes subpopulations in cerebro-spinal fluid (CSF) and peripheral blood (PB) from multiple sclerosis (MS) patients were studied. PB of MS patients contains the same prevalence of E and EA rosette forming cells compared with controls, consisting of patients affected by various "nonimmunological" neuropsychiatric diseases. Cytochemical identification by the method of acid esterases in PB demonstrated in MS a prevalence of lymphocyte subpopulations similar to controls, and a relatively high percentage of macrophages compared with other methods, especially in MS patients: this may partially account for variable results obtained by various authors with the rosette technique. In CSF a significant decrease of total T, and particularly of T gamma cells, was found. Since T gamma lymphocytes have a suppressor effect on B cell proliferation and Ig synthesis, their decrease could be related with Ig hypersynthesis commonly found in the central nervous system of MS patients.

Analysis of lymphocyte subpopulations in cerebrospinal fluid and peripheral blood in patients with multiple sclerosis and inflammatory diseases of the nervous system.

We analysed different subsets of lymphocytes from peripheral blood (PB) and cerebrospinal fluid (CSF) by flow cytometry in order to determinate alterations in patients with multiple sclerosis (MS) in acute relapse and viral inflammatory neurological disease (IND). We found increased levels of adhesion molecules (LFA-1 and beta1 integrin) in the CSF of patients with MS and IND compared to NIND. CD4+/CD8+ ratio was significantly higher in CSF of MS as compared with all groups analysed and compared with PB. We detected a significantly higher expression of the interleukin-2 receptor in PB of MS patients when compared with other groups. In patients with IND a significant higher expression of the interleukin-2 receptor was found in the CSF compared with MS and NIND. Our findings indicate that the activation of T lymphocytes primarily occurs in the peripheral immune compartment in MS and the increase of adhesion molecules in CSF is related to inflammatory disorders and not only to MS.

Lymphocyte phenotype and subset distribution in normal cerebrospinal fluid

The distribution of lymphocyte subpopulations in cerebrospinal fluid (CSF) and their phenotypic characteristics were extensively investigated in a group of 18 healthy individuals using two- and three-color flow cytometry. Generally, CDS + T lymphocytes constituted the vast majority of CSF lymphocytes while the number of B lymphocytes and NK cells were low. Most T lymphocytes exhibited the phenotype of memory /primed cells in both the CD4 + and CD8 + subpopulations. Two markers for recent activation, HLA-DR and interleukin-2 receptor (CD25) were not upregulated when compared with peripheral blood (PB) in the majority of CSF T lymphocytes. However, a fraction of T lymphocytes co-expressing the NK cell markers CD56 and/or CD16 showed a pronounced upregulation of HLA-DR in CSF as compared with PB. This study documents that the cellular composition of the normal CSF differs profoundly from PB regarding all major lymphocyte subpopulations. This has to be taken into account in studies addressing questions regarding cellular immune reactions in the central nervous system under pathological conditions.