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HLA-B7-restricted EBV-specific CD8+ T cells are dysregulated in multiple sclerosis.
J Immunol 2012; 188(9):4671-80JI

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.

Authors+Show Affiliations

Division of Immunology and Allergy, Department of Medicine, University Hospital of Lausanne, 1011 Lausanne, Switzerland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22461701

Citation

Jilek, Samantha, et al. "HLA-B7-restricted EBV-specific CD8+ T Cells Are Dysregulated in Multiple Sclerosis." Journal of Immunology (Baltimore, Md. : 1950), vol. 188, no. 9, 2012, pp. 4671-80.
Jilek S, Schluep M, Harari A, et al. HLA-B7-restricted EBV-specific CD8+ T cells are dysregulated in multiple sclerosis. J Immunol. 2012;188(9):4671-80.
Jilek, S., Schluep, M., Harari, A., Canales, M., Lysandropoulos, A., Zekeridou, A., ... Du Pasquier, R. A. (2012). HLA-B7-restricted EBV-specific CD8+ T cells are dysregulated in multiple sclerosis. Journal of Immunology (Baltimore, Md. : 1950), 188(9), pp. 4671-80. doi:10.4049/jimmunol.1103100.
Jilek S, et al. HLA-B7-restricted EBV-specific CD8+ T Cells Are Dysregulated in Multiple Sclerosis. J Immunol. 2012 May 1;188(9):4671-80. PubMed PMID: 22461701.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - HLA-B7-restricted EBV-specific CD8+ T cells are dysregulated in multiple sclerosis. AU - Jilek,Samantha, AU - Schluep,Myriam, AU - Harari,Alexandre, AU - Canales,Mathieu, AU - Lysandropoulos,Andreas, AU - Zekeridou,Anastasia, AU - Pantaleo,Giuseppe, AU - Du Pasquier,Renaud A, Y1 - 2012/03/28/ PY - 2012/3/31/entrez PY - 2012/3/31/pubmed PY - 2012/6/12/medline SP - 4671 EP - 80 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J. Immunol. VL - 188 IS - 9 N2 - 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. SN - 1550-6606 UR - https://www.unboundmedicine.com/medline/citation/22461701/HLA_B7_restricted_EBV_specific_CD8+_T_cells_are_dysregulated_in_multiple_sclerosis_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=22461701 DB - PRIME DP - Unbound Medicine ER -