Cerebrospinal Fluid Mononuclear Cells Research Articles

Inflammatory cerebrospinal fluid t cells have activation requirements characteristic of cd4+cd45ra‐ t cells

It has long been recognized that T cells in the cerebrospinal fluid (CSF) and other inflammatory compartments cannot be stimulated by mitogen and the reason for this has remained unknown. This question was investigated using mononuclear cells (MNC) isolated from the CSF of subjects with multiple sclerosis and other inflammatory brain diseases which predominantly express the CD4 and CDw29 but not CD45RA determinants. CSF and blood cells were stimulated by either the CD3/T cell receptor complex, the CD2 activation pathway, calcium ionophore, or an activator of protein kinase C, phorbol myristate acetate (PMA). CSF MNC proliferated less than blood MNC following stimulation by phytohemagglutinin in subjects with inflammation in the CSF, but not in subjects with non-inflammatory CNS diseases. Moreover, CSF MNC were not induced to proliferate through stimulation of the CD2 pathway by anti-T11(2) + anti-T11(3) monoclonal antibodies (mAb). This was not due to defects in either interleukin 2 receptors, interleukin 2 secretion, or to T cell pre-activation in vivo. Instead, the refractory activation state of inflammatory CSF T cells was corrected by PMA. That CSF contains predominantly CD4+CDw29+CD45RA- cells suggests that PMA may be co-stimulatory with anti-CD2 mAb to activate this population of T cells. This was confirmed in experiments with sorted T cells from normal subjects. These data suggest that the inability of mitogens or anti-CD2 mAb to stimulate inflammatory CSF T cells, which can be corrected by an inducer of protein kinase C, is related to the relative absence of CD4+CD45RA+ cells in the CSF. Alterations of protein kinase C and protein phosphorylation may exist in inflammatory T cell populations that regulate the immune response.

Mononuclear Cell Types in Cerebrospinal Fluid and Blood of Patients With Multiple Sclerosis

Phenotypic distribution of mononuclear cells in cerebrospinal fluid (CSF) and peripheral blood from patients with multiple sclerosis (MS) and, for reference, patients with acute aseptic meningoencephalitis (AM), and in blood only from healthy controls, was studied with an immunoenzymatic microassay enabling analysis even in the presence of a normal CSF cell count. In MS, increased CD5+ (pan-T) cell proportion in CSF compared with blood was not reflected by changes of CD4+ or CD8+ cells, while in AM, an increase of CD4+ cells was registered. Therefore, a population of CD5+, CD4-, and CD8- cells may be anticipated to exist in CSF of patients with MS. Numbers of OKB7+, OKM1+, or HLA-DR+ cells did not distinguish between MS and AM. Proliferating cells expressing transferrin receptors (OKT9+ cells) were generally few or absent in CSF and not useful as a marker of disease activity in either MS or AM.

Identification of mononuclear cells in CSF of patients with HIV infection

Using immunocytochemical methods, CSF lymphocyte subpopulations were examined in different neurologic disorders associated with human immunodeficiency virus (HIV) infection. CSF pleocytosis was observed in asymptomatic neurologically normal subjects, in patients with aseptic meningitis, and those with inflammatory demyelinating neuropathies, but infrequently in subjects with AIDS dementia complex. The distribution of CSF lymphocyte subpopulations in HIV-infected patients differed from control subjects showing decreases in percentages of T helper (CD4) cells and increases in T suppressor (CD8) cells. Peripheral blood and CSF CD4:CD8 ratios were inverted in all of the neurologic disorders studied. In all disorders, the changes in CSF composition of mononuclear cells paralleled alterations in peripheral blood and in patients with AIDS dementia complex, there was a relationship between the severity of dementia and blood and CSF CD4 lymphocyte proportions.

Diagnosis of CNS lymphoma using immunofluorescent phenotyping of CSF mononuclear cells

We describe the use of a panel of monoclonal antibodies, directed against leukocyte surface antigens to characterize CSF mononuclear cells with regard to malignancy when cytopathology was inconclusive. Cytocentrifuged preparations from three patients in which traditional modalities had not yielded a diagnosis were studied, utilizing a panel of antibodies for B and T cell antigens. All three patients were found to have B cell lymphoma of the CNS. Rapid institution of the appropriate therapy resulted in marked improvement of CNS symptoms in each case. Our results indicate that in patients with CNS disease and CSF pleocytosis of undefined nature, this technique may provide rapid and precise diagnostic information.

Response to and production of interleukin 2 by peripheral blood and cerebrospinal fluid lymphocytes of patients with multiple sclerosis.

In an effort to further characterize the defective proliferative response of T lymphocytes to mitogens in multiple sclerosis (MS) patients, we examined the response to and production of interleukin 2 (IL 2) by both peripheral blood lymphocytes (PBL) and cerebrospinal fluid mononuclear cells. We also examined the proportion of cells bearing receptors for IL 2 and transferrin. Chronic progressive MS patients have an abnormally low response to exogenous IL 2 as compared to controls. Whereas acute relapse patients' PBL demonstrated a normal IL 2 response during an exacerbation, they showed reduced responsiveness during remission. These abnormalities could not be explained by different dose or kinetic response optima to PHA or IL 2, nor could they be explained by depressed numbers of IL 2 or transferrin receptor-bearing lymphocytes. Production of IL 2 by PBL was also abnormal in MS patients. Chronic progressive patients produced elevated levels of IL 2, whereas acute relapse patients undergoing an exacerbation produced diminished levels of IL 2. During remission, these levels returned to that of controls'. The effect of 1200 rad x-irradiation or nylon wool removal of adherent cells was a significantly greater augmentation of IL 2 production in MS patients than in other neurologic disease or normal controls. Cerebrospinal fluid lymphocytes from MS patients had normal proportions of IL 2 receptor-bearing cells, but were deficient in their IL 2 response and production as compared to autochthonous or control PBL. The inability of some MS patients' lymphocytes to clonally expand in response to IL 2 might contribute to the pathogenicity of the disease.

Spontaneous proliferation of cerebrospinal fluid mononuclear cells in multiple sclerosis: A longitudinal study

Cerebrospinal fluid (CSF) and peripheral blood (PB) specimens from 32 MS patients longitudinally followed for up to 24 months and from a group of control patients without intrathecal inflammation were studied for the occurrence of activated lymphocytes with an autoradiography method. MS patients had higher numbers of proliferating mononuclear cells in CSF than did the controls, both during remission and exacerbation phases, whereas this difference was not found in the PB. ACTH treatment decreased the number of proliferating cells in CSF but had no effect on those of the PB of MS patients. A large variation in spontaneous proliferation of CSF cells was evident during the follow-up of individual patients, and there seemed to be no uniform correlation to the clinical fluctuations.

'Doctor's Orders'

CSF Analyses Time of Lumbar Puncture Opening Pressure, mm HO CSF Glucose, mg/dL CSF Protein, mg/dL CSF WBC Count, Cells/cu mm CSF Neutrophils, % CSF Mononuclear Cells, % Admission 210 71 300 5,000 50 50 monocytes 8 hr after admission 210 168 600 62 11 monocytes 27 lymphocytes 4 days after admission 75 67 27 10 90 lymphocytes 6 days after admission 70 54 100 lymphocytes To the Editor. —Ethical attitudes about and toward medical care have changed. Those most concerned can scarcely keep abreast of the relevant publications and seminars. A myriad of scientific and social developments have converged in such a manner that patients, health-care providers, scientists, government personnel, philosophers, ethicists, social workers, private foundations, and politicians provide sources of ideas about what may be wrong ethically and what should be changed in patient care. There is little question that biomedical ethical attitudes must be reanalyzed very critically. One of

Proliferating cells in demyelinating states.

Proliferation of mononuclear cells was examined with an autoradiography method in the CSF and peripheral blood of 13 patients with multiple sclerosis (MS), serially during activation of disease in one patient with subacute sclerosis panencephalitis (SSPE), and in some control patients with various neurological conditions. High cerebrospinal fluid (CSF) cell labelling indices, up to 1.7%, which could not be directly related to the clinical activity of the disease, were found in some MS patients. During activation of SSPE there was marked increase in labelled cells of CSF, up to 4.3%. In controls, corresponding CSF indices ranged from less than 0.1% to 0.4%. Mononuclear cells in CSF and peripheral blood behaved as clearly different cell populations.

Lymphocytic infiltration of the brain in sleeping sickness.

Cerebrospinal fluid mononuclear cells from 40 patients with advanced Gambian sleeping sickness were examined for intracytoplasmic immunoglobulin and for B- and T-lymphocyte markers. About 5% of mononuclear cells were plasma cells. Most of the lymphocytes present were B cells. These findings suggest that the considerable lymphocytic infiltration of the nervous system seen in advanced sleeping sickness is not a cell-mediated immune reaction to trypanosomes. Immune complexes may play a part in producing the brain damage characteristic of this disease.

Partial antibiotic therapy in Haemophilus infuenzae meningitis. Its effect on cerebrospinal fluid abnormalities.

To examine the influence of partial antibiotic therapy on laboratory findings in Haemophilus influenzae meningitis, 272 untreated cases and 202 partially treated, culture-positive cases from 1953 through 1971 were reviewed. There was no significant difference between the two groups with respect to several cerebrospinal fluid (CSF) values. Both the untreated and partially treated groups had a similar proportion of cases with negative Gram stain and CSF glucose level over 40 mg/100 ml or a predominance of CSF mononuclear cells. Eight patients had received ampicillin sodium, chloramphenicol, or tetracycline for two days or more. The CSF findings of these patients resembled those of the untreated group. The data support the conclusion that antibiotics in the usual outpatient dosages seldom interfere with the diagnosis of H influenzae meningitis.

Thymidine Kinase Activity in Cerebrospinal Fluid of Rabbits with Herpesvirus hominis Encephalitis

The rabbit model of Herpesvirus hominis (HVH) encephalitis was utilized to determine whether thymidine (TdR) kinase (EC. 2.7.1.2.1), AN EARLY ENZYME IN THe HVH replicative cycle, is present in the cerebrospinal fluid (CSF) of rabbits with HVH encephalitis. The mean TdR kinase activity in CSF from infected rabbits was 2.30 plus or minus 1.69 pmol product/120 min/100 mul CSF, while the mean TdR kinase activity of uninfected CSF was 0.34 plus or minus 0.25. The enzyme appeared to be cell associated since the TdR kinase activity in the sedimented cell suspension was 5.08 plus or minus 2.93 (seven values) while the supernatant activity was 0.14 plus or minus 0.31 (seven values). To allow a comparison of TdR kinase from infected rabbit CSF with HVH and rabbit mononuclear cell TdR kinase, the mean ratio of TdR kinase activity at pH 6.0/pH 8.0, for infected rabbit CSF is intermediate between the ratio for HVH TdR kinase (P less than 0.001) and rabbit mononuclear cell TdR kinase (P less than 0.05).