Article

HLA-B7-restricted EBV-specific CD8+ T cells are dysregulated in multiple sclerosis.

Division of Immunology and Allergy, Department of Medicine, University Hospital of Lausanne, 1011 Lausanne, Switzerland.
The Journal of Immunology (impact factor: 5.79). 03/2012; 188(9):4671-80. DOI:10.4049/jimmunol.1103100 pp.4671-80
Source: PubMed

ABSTRACT It was hypothesized that the EBV-specific CD8(+) T cell response may be dysregulated in multiple sclerosis (MS) patients, possibly leading to a suboptimal control of this virus. To examine the CD8(+) T cell response in greater detail, we analyzed the HLA-A2-, HLA-B7-, and HLA-B8-restricted EBV- and CMV-specific CD8(+) T cell responses in a high number of MS patients and control subjects using tetramers. Content in cytolytic granules, as well as cytotoxic activity, of EBV- and CMV-specific CD8(+) T cells was assessed. We found that MS patients had a lower or a higher prevalence of HLA-A2 and HLA-B7, respectively. Using HLA class I tetramers in HLA-B7(+) MS patients, there was a higher prevalence of MS patients with HLA-B*0702/EBV(RPP)-specific CD8(+) T cells ex vivo. However, the magnitude of the HLA-B*0702/EBV(RPP)-specific and HLA-B*0702/CMV(TPR)-specific CD8(+) T cell response (i.e., the percentage of tetramer(+) CD8(+) T cells in a study subject harboring CD8(+) T cells specific for the given epitope) was lower in MS patients. No differences were found using other tetramers. After stimulation with the HLA-B*0702/EBV(RPP) peptide, the production of IL-2, perforin, and granzyme B and the cytotoxicity of HLA-B*0702/EBV(RPP)-specific CD8(+) T cells were decreased. Altogether, our findings suggest that the HLA-B*0702-restricted viral (in particular the EBV one)-specific CD8(+) T cell response is dysregulated in MS patients. This observation is particularly interesting knowing that the HLA-B7 allele is more frequently expressed in MS patients and considering that EBV is associated with MS.

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    Article: Increased CD8+ T Cell Response to Epstein-Barr Virus Lytic Antigens in the Active Phase of Multiple Sclerosis
    Angelini DF, Serafini B, Piras E, Severa M, Coccia EM, Rosicarelli B, Ruggieri S, Gasperini C, Buttari F, Centonze D, Mechelli R, Salvetti M, Borsellino G, Aloisi F, Battistini L
    [show abstract] [hide abstract]
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    PLoS Pathogens 04/2013; 9(4):1. · 9.13 Impact Factor
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Keywords

CMV-specific CD8(+)
 
control subjects
 
EBV
 
EBV one)-specific CD8(+
 
EBV-
 
EBV-specific CD8(+)
 
given epitope
 
granzyme B
 
greater detail
 
higher prevalence
 
HLA-A2
 
HLA-A2-
 
HLA-B*0702-restricted viral
 
HLA-B8-restricted EBV-
 
IL-2
 
lower
 
MS patients
 
multiple sclerosis
 
stimulation
 
study subject harboring CD8(+)