T-cells in the cerebrospinal fluid express a similar repertoire of inflammatory chemokine receptors in the absence or presence of CNS inflammation: implications for CNS trafficking - PubMed (original) (raw)

T-cells in the cerebrospinal fluid express a similar repertoire of inflammatory chemokine receptors in the absence or presence of CNS inflammation: implications for CNS trafficking

P Kivisäkk et al. Clin Exp Immunol. 2002 Sep.

Abstract

It is believed that chemokines and their receptors are involved in trafficking of T-cells to the central nervous system (CNS). The aim of the current study was to define the expression on cerebrospinal fluid (CSF) T-cells of six chemokine receptors associated with trafficking to sites of inflammation. Flow cytometry was used to detect chemokine receptor expression. We observed that CD3+T-cells in the CSF express a restricted array of inflammatory chemokine receptors, specifically CXCR3, CCR5 and CCR6, but little CCR1-3. This repertoire was independent of the presence of CNS inflammation, since comparable findings were obtained in patients with multiple sclerosis (MS) and individuals with non-inflammatory neurological diseases. The enrichment of CCR5+T-cells in the CSF could largely be explained by higher frequency of CD4+/CD45RO+T-cells in this compartment. In contrast, CD4+/CD45RO+T-cells expressing CXCR3 were significantly enriched in CSF as compared with blood. Similar levels of CCR6+/CD3+T-cells were observed in blood and CSF, while levels of CCR2+/CD3+T-cells were lower in CSF than in blood. The CSF was virtually devoid of CCR5+/CXCR3- T-cells, suggesting that the expression of CCR5 alone is not sufficient for the trafficking of CD3+T-cells to the CSF. We hypothesize that CXCR3 is the principal inflammatory chemokine receptor involved in intrathecal accumulation of T-cells in MS. Through interactions with its ligands, CXCR3 is proposed to mediate retention of T-cells in the inflamed CNS.

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Figures

Fig. 1

Fig. 1

Chemokine receptor expression on CD3+T-cells was compared in stainings of whole blood, followed by selective erythrocyte lysis, performed at RT (□) and +4°C (formula image), and in stainings of PBMCs performed at RT (▪). Figure shows mean +SD of three healthy donors.

Fig. 2

Fig. 2

Cells from peripheral blood (PB) and CSF were gated according to forward- and side light scattering properties, and were positively selected for CD3 expression. Histograms for each chemokine receptor on CSF T-cells (——) are shown overlaid on the paired staining of PB T-cells (–––––) from the same donor. Isotype matched control moAbs were used for each chemokine receptor.

Fig. 3

Fig. 3

Chemokine receptor expression was determined on CD3+T-cells in peripheral blood (PB) and CSF from patients with inflammatory CNS demyelination (manifested as MS (21 patients), a clinically isolated syndrome suggestive of MS (10 patients), or recurrent multicentric myelitis (1 patient); (○) and control individuals with non-inflammatory neurological disorders (NIND; •) using flow cytometry. Lines connect paired blood and CSF samples from individual patients.

Fig. 4

Fig. 4

Co-expression of CXCR3 and CCR5 on individual T-cells in (a) peripheral blood and (b) CSF was compared using three-colour flow cytometry. Cells were gated according to forward- and side-light scattering properties, and were positively selected for CD3 expression.

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