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Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
Published on: February 8, 2018
Increased expression of PD-1 in CD8 + CD3 + T cells correlates with EBV viral load in MS patients
Atefeh Najmadini1, Mohammad Mahdi Mohammadi2, Ladan Langroudi1
1Department of Medical Immunology, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
Abstract:
Multiple sclerosis (MS) is one of the common autoimmune diseases. The exact etiology of MS is still unclear, but recent studies have shown the possibility of infectious agent involvement such as Epstein-Barr virus (EBV) in MS pathophysiology. In this study, CD3 + CD8 + T cells of 25 new case MS patients were compared with healthy donors for expression of exhaustion marker, PD-1, using flow cytometry. Also, the expression of the EBV gene, BRCF-1, in PBMCs was analyzed using real-time PCR. Results revealed a lower frequency of CD3 + CD8 + T cells in MS patients. Also, increased expression of PD-1 was observed on CTLs which correlated with higher viral loads. Therefore, a lower frequency of CD8 + T cells but a higher exhaustion marker in MS patients reveals a new mechanism of EBV pathogenesis in MS development. The results suggest that inefficient immune control of EBV in patients with MS may cause exacerbation of the disease. Future studies on the mechanism of T cell exhaustion and chronic infections may aid in a better understanding of the disease and the design of effective therapies.
Insights
Multiple sclerosis (MS) patients show reduced CD8+ T cells and increased PD-1 exhaustion markers, suggesting Epstein-Barr virus (EBV) contributes to MS pathogenesis through impaired immune control.
Area of Science:
- Immunology
- Neuroscience
- Infectious Diseases
Background:
- Multiple sclerosis (MS) is a prevalent autoimmune disease with an unclear etiology.
- Emerging evidence suggests infectious agents, like Epstein-Barr virus (EBV), may play a role in MS pathophysiology.
- Understanding immune dysregulation in MS is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the frequency of CD8+ T cells and PD-1 expression in MS patients.
- To analyze Epstein-Barr virus (EBV) gene expression in patients with MS.
- To explore the potential link between EBV infection, T cell exhaustion, and MS development.
Main Methods:
- Flow cytometry was used to compare CD3+CD8+ T cells and PD-1 expression in 25 new MS cases versus healthy donors.
- Real-time PCR analyzed Epstein-Barr virus (EBV) gene BRCF-1 expression in peripheral blood mononuclear cells (PBMCs).
Main Results:
- MS patients exhibited a lower frequency of CD3+CD8+ T cells compared to healthy controls.
- Increased expression of the exhaustion marker PD-1 was observed on CD8+ T cells (CTLs) in MS patients.
- Elevated PD-1 expression on CTLs correlated with higher Epstein-Barr virus (EBV) viral loads.
Conclusions:
- A reduced CD8+ T cell count coupled with heightened T cell exhaustion (PD-1+) in MS patients points to a novel EBV pathogenesis mechanism.
- Inefficient immune surveillance of EBV in MS patients may exacerbate disease progression.
- Further research into T cell exhaustion and chronic infections is vital for advancing MS understanding and therapy.

