Expression of Chemokine Receptors on Th1/Th2 CD4+ Lymphocytes in Patients with Multiple Sclerosis
Alireza Andalib1, Hassan Doulabi, Mohamadreza Najafi
1Department of Immunology, Isfahan Medical School, Isfahan University of Medical Sciences, Isfahan, Iran. Andalib@med.mui.ac.ir
Insights
Interferon-beta therapy shifts T-helper cell balance in Multiple Sclerosis (MS) patients from a Th1 to a Th2 dominant state. Monitoring chemokine receptor expression on CD4 T cells can help evaluate MS disease status.
Area of Science:
- Immunology
- Neuroscience
- Cell Biology
Background:
- Multiple Sclerosis (MS) is a T-helper 1 (Th1) cell-dependent inflammatory disease of the central nervous system.
- Th1 cells express CXCR3, CCR5, and CCR6, while Th2 cells express CCR3 and CCR4.
- Immunomodulatory cytokines can alter chemokine receptor expression patterns on lymphocyte subsets.
Purpose of the Study:
- To measure chemokine receptor expression on CD4 T cells in Multiple Sclerosis (MS) patients.
- To evaluate the shift in Th1/Th2 dominance following Interferon-beta (IFN-β) treatment in MS patients.
Main Methods:
- Flow cytometry was used to detect chemokine receptor expression on CD4 T cells.
- Peripheral blood mononuclear cells (PBMCs) were analyzed from 26 MS patients before and after IFN-β therapy, and from a healthy control group.
Main Results:
- MS patients showed altered lymphocyte percentages compared to controls.
- CD4+CXCR3+ cells were significantly higher in pre-treated MS patients than in healthy controls, decreasing after IFN-β treatment.
- CD4+CCR4+ cell subsets became dominant after IFN-β therapy, indicating a shift towards a Th2 response.
- A strong association was found between pre- and post-treatment CXCR3 and CCR4 expression.
Conclusions:
- IFN-β treatment induces a shift from Th1 to Th2 dominance in MS patients.
- Chemokine receptor expression patterns on Th1/Th2 cell subsets can serve as a biomarker for monitoring MS disease status and treatment efficacy.
Background:
Th1 cells preferentially express CXCR3, CCR5 and CCR6, while CCR3 and CCR4 are predominantly expressed by Th2 cell subsets. Multiple Sclerosis (MS) is a Th1 cell-dependant chronic inflammatory disease of the central nervous system, and immunomudolatory cytokines could alter the chemokine expression pattern of these lymphocyte subsets.
Objective:
This study was performed to measure chemokine receptor expression on CD4 T cells for evaluation of Th1/Th2 dominantly in IFN-β treated patients.
Methods:
Flowcytometry was used to detect chemokine receptor expression on CD4 T cell population in PBMCs obtained from MS and healthy control groups. Twenty six MS patients participated in this study before and after IFN-β therapy and the same number of healthy individuals were included.
Results:
The percentage of lymphocytes was 41.28% ± 10.30% 2 in the blood of MS group compared with 36.88% ± 5.51% in the control group (p=0.017). The CD4+CXCR3+ cells were 18.86% ± 8.46% in healthy group, 30.78% ± 9.8% in pre-treated MS patients and 21.06% ± 9.23% in post-treated group (p<0.001). The CD4+CCR4+ cell subsets were 27.35% ± 10.15% in healthy group; 28.17% ± 8.9% in pre-treated group and 34.20% ± 8.96% in the post-IFN-β treatment group. The subset of CD4+CCR4+ was found to be dominant after IFN-β therapy in comparison with the control group (p<0.001). CD4+CCR5+ percentage was 1.24% ± 0.92% in the healthy people, 1.23% ± 0.71% in the MS patients and 0.76% ± 0.49% in post-treatment status (p=0.003). CD4+CCR3+ cell subsets were 0.62% ± 0.67% in control group, 0.28% ± 0.26% in the MS patients (p=0.022) and 0.39% ± 0.54% in IFN-β treated patients (p=0.334). An association was found for CXCR3 expression in pre- and post-treatment status (r=0.840, p<0.001) as well as for CCR4+ expression (r=0.712, p<0.001) in the same groups. The Th1 response was dominant in pre-treatment states, and then it shifted to a Th2 dominant state after IFN-β treatment.
Conclusion:
We suggest that the chemokine receptor expression of Th1/Th2 cell subsets could be used for monitoring and the evaluation of the MS disease status.
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