Central memory CD4+ T cells dominate the normal cerebrospinal fluid

Graaf, Marloes Thoomes-de; Smitt, Peter A.E. Sillevis; Luitwieler, Ronald L.; Velzen, Chris van; Broek, Patricia D. M. van den; Kraan, Jaco; Gratama, Jan W.

doi:10.1002/cyto.b.20542

Cited by 123 publications

(108 citation statements)

References 28 publications

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“…In contrast, the few immune cells circulating in the CSF are mostly T cells with a ratio of CD4 + T cells to CD8 + T cells of about 3.5 to 1 (summarized in [113]). The population of T cells found in the CSF of the ventricles and subarachnoid space contains mostly memory T cells that have characteristics of central memory T cells (T CM cells) and effector memory T cells (T EM cells) [33,123]. Animal models have provided additional evidence for the presence of yet another subset of memory T cells in the CNS that do not recirculate but rather persist in the CSF-drained spaces after previous infections [165].…”

Section: Neuroimmune Function Of the Choroid Plexuses In Healthmentioning

confidence: 99%

Molecular anatomy and functions of the choroidal blood-cerebrospinal fluid barrier in health and disease

et al. 2018

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The barrier between the blood and the ventricular cerebrospinal fluid (CSF) is located at the choroid plexuses. At the interface between two circulating fluids, these richly vascularized veil-like structures display a peculiar morphology explained by their developmental origin, and fulfill several functions essential for CNS homeostasis. They form a neuroprotective barrier preventing the accumulation of noxious compounds into the CSF and brain, and secrete CSF, which participates in the maintenance of a stable CNS internal environment. The CSF circulation plays an important role in volume transmission within the developing and adult brain, and CSF compartments are key to the immune surveillance of the CNS. In these contexts, the choroid plexuses are an important source of biologically active molecules involved in brain development, stem cell proliferation and differentiation, and brain repair. By sensing both physiological changes in brain homeostasis and peripheral or central insults such as inflammation, they also act as sentinels for the CNS. Finally, their role in the control of immune cell traffic between the blood and the CSF confers on the choroid plexuses a function in neuroimmune regulation and implicates them in neuroinflammation. The choroid plexuses, therefore, deserve more attention while investigating the pathophysiology of CNS diseases and related comorbidities.

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Section: Neuroimmune Function Of the Choroid Plexuses In Healthmentioning

confidence: 99%

Molecular anatomy and functions of the choroidal blood-cerebrospinal fluid barrier in health and disease

et al. 2018

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“…These APCs are present at low levels in the CSF, (116) or are situated in the meninges, choroid plexus, perivascular space, or brain parenchyma as astrocytes and microglial cells (92,160). Major pattern recognition receptors involved in initial sensing of pneumococci in the CNS are TLR2 (133,248), TLR4 (245), TLR9 (10), and Nod-like receptors (NLRs) (Fig.…”

Section: Pattern Recognition Receptorsmentioning

confidence: 99%

Pathogenesis and Pathophysiology of Pneumococcal Meningitis

et al. 2011

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SUMMARY Pneumococcal meningitis continues to be associated with high rates of mortality and long-term neurological sequelae. The most common route of infection starts by nasopharyngeal colonization by Streptococcus pneumoniae , which must avoid mucosal entrapment and evade the host immune system after local activation. During invasive disease, pneumococcal epithelial adhesion is followed by bloodstream invasion and activation of the complement and coagulation systems. The release of inflammatory mediators facilitates pneumococcal crossing of the blood-brain barrier into the brain, where the bacteria multiply freely and trigger activation of circulating antigen-presenting cells and resident microglial cells. The resulting massive inflammation leads to further neutrophil recruitment and inflammation, resulting in the well-known features of bacterial meningitis, including cerebrospinal fluid pleocytosis, cochlear damage, cerebral edema, hydrocephalus, and cerebrovascular complications. Experimental animal models continue to further our understanding of the pathophysiology of pneumococcal meningitis and provide the platform for the development of new adjuvant treatments and antimicrobial therapy. This review discusses the most recent views on the pathophysiology of pneumococcal meningitis, as well as potential targets for (adjunctive) therapy.

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“…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). 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).…”

Section: Cellular Composition Of Normal Csfmentioning

confidence: 99%

Flow cytometric characterization of cerebrospinal fluid cells

Graaf

Jongste

Kraan

et al. 2011

Cytometry Part B Clinical

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120

115

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Flow cytometry facilitates the detection of a large spectrum of cellular characteristics on a per cell basis, determination of absolute cell numbers and detection of rare events with high sensitivity and specificity. White blood cell (WBC) counts in cerebrospinal fluid (CSF) are important for the diagnosis of many neurological disorders. WBC counting and differential can be performed by microscopy, hematology analyzers, or flow cytometry. Flow cytometry of CSF is increasingly being considered as the method of choice in patients suspected of leptomeningeal localization of hematological malignancies. Additionally, in several neuroinflammatory diseases such as multiple sclerosis and paraneoplastic neurological syndromes, flow cytometry is commonly performed to obtain insight into the immunopathogenesis of these diseases. Technically, the low cellularity of CSF samples, combined with the rapidly declining WBC viability, makes CSF flow cytometry challenging. Comparison of flow cytometry with microscopic and molecular techniques shows that each technique has its own advantages and is ideally combined. We expect that increasing the number of flow cytometric parameters that can be simultaneously studied within one sample, will further refine the information on CSF cell subsets in low-cellular CSF samples and enable to define cell populations more accurately. V C 2011 International Clinical Cytometry Society

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Central memory CD4+ T cells dominate the normal cerebrospinal fluid

Cited by 123 publications

References 28 publications

Molecular anatomy and functions of the choroidal blood-cerebrospinal fluid barrier in health and disease

Molecular anatomy and functions of the choroidal blood-cerebrospinal fluid barrier in health and disease

Pathogenesis and Pathophysiology of Pneumococcal Meningitis

Flow cytometric characterization of cerebrospinal fluid cells

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