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Published on: May 8, 2016
Multiple sclerosis and optic neuritis: CCR5 and CXCR3 expressing T cells are augmented in blood and cerebrospinal
Natalia Teleshova1, Mikhail Pashenkov, Yu-Min Huang
1Department of Neurology, Karolinska Institutet, Huddinge University Hospital, 14186 Stockholm, Sweden.
Abstract:
A role for chemokines as mediators of Th1 cell recruitment to the central nervous system (CNS) is probable in MS. Therefore we studied expression of Th1-related CCR5 and CXCR3 chemokine receptors in patients with MS and controls. Patients with untreated MS had elevated percentages of CCR5 and CXCR3 expressing T cells vs. healthy controls (HC) in blood, and vs. other non-inflammatory neurological diseases (OND) patients in CSF. Such elevation was not found in MS patients examined during ongoing treatment with IFN-beta. Patients with optic neuritis (ON), a common first manifestation of MS, had elevated percentages of CXCR3 expressing T cells in blood compared with HC, and of CCR5 expressing T cells in CSF compared with OND patients. High chemokine receptor expression may be one prerequisite for Th1 cells to migrate to the CNS. Inhibition of chemokine receptor expression may constitute a potentially important therapeutic effect of IFN-beta.
Insights
Chemokine receptors CCR5 and CXCR3 are elevated in T cells of untreated multiple sclerosis (MS) patients, suggesting a role in central nervous system (CNS) invasion. Interferon-beta treatment may reduce this expression.
Area of Science:
- Neuroimmunology
- Molecular immunology
- Cellular immunology
Background:
- Chemokines are implicated in T-cell recruitment to the central nervous system (CNS) in multiple sclerosis (MS).
- Understanding chemokine receptor expression is crucial for elucidating T-cell migration in MS pathogenesis.
Purpose of the Study:
- To investigate the expression of Th1-related chemokine receptors CCR5 and CXCR3 in patients with MS.
- To compare receptor expression in MS patients with healthy controls (HC) and other non-inflammatory neurological disease (OND) patients.
- To assess the impact of interferon-beta (IFN-beta) treatment and optic neuritis (ON) on chemokine receptor expression.
Main Methods:
- Flow cytometry was used to quantify T cells expressing CCR5 and CXCR3.
- Analysis was performed on blood samples from MS patients, HC, and OND patients.
- Cerebrospinal fluid (CSF) samples were analyzed from MS and OND patients.
Main Results:
- Untreated MS patients showed higher percentages of CCR5 and CXCR3 expressing T cells in blood compared to HC.
- Elevated CCR5 and CXCR3 expressing T cells were observed in CSF of MS patients versus OND patients.
- MS patients undergoing IFN-beta treatment did not exhibit these elevated receptor percentages.
- Patients with optic neuritis (ON) had increased CXCR3+ T cells in blood and CCR5+ T cells in CSF.
Conclusions:
- Elevated CCR5 and CXCR3 expression on T cells may facilitate their migration into the CNS in MS.
- IFN-beta treatment might exert a therapeutic effect by inhibiting chemokine receptor expression.
- Chemokine receptor expression patterns in ON suggest early involvement in MS pathogenesis.
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