NS1 specific CD8+ T-cells with effector function and TRBV11 dominance in a patient with parvovirus B19 associated inflammatory cardiomyopathy

Streitz, M, Noutsias, M, Volkmer, R, Rohde, M, Brestrich, G, Block, A, Klippert, K, Kotsch, K, Ay, B, Hummel, M, Kuhl, U, Lassner, D, Schultheiss, H P, Volk, H D and Kern, F (2008) NS1 specific CD8+ T-cells with effector function and TRBV11 dominance in a patient with parvovirus B19 associated inflammatory cardiomyopathy. PloS ONE, 3 (6). e2361. ISSN 1932-6203

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Abstract

BACKGROUND: Parvovirus B19 (B19V) is the most commonly detected virus in endomyocardial biopsies (EMBs) from patients with inflammatory cardiomyopathy (DCMi). Despite the importance of T-cells in antiviral defense, little is known about the role of B19V specific T-cells in this entity. METHODOLOGY AND PRINCIPAL FINDINGS: An exceptionally high B19V viral load in EMBs (115,091 viral copies/mug nucleic acids), peripheral blood mononuclear cells (PBMCs) and serum was measured in a DCMi patient at initial presentation, suggesting B19V viremia. The B19V viral load in EMBs had decreased substantially 6 and 12 months afterwards, and was not traceable in PBMCs and the serum at these times. Using pools of overlapping peptides spanning the whole B19V proteome, strong CD8(+) T-cell responses were elicited to the 10-amino-acid peptides SALKLAIYKA (19.7% of all CD8(+) cells) and QSALKLAIYK (10%) and additional weaker responses to GLCPHCINVG (0.71%) and LLHTDFEQVM (0.06%). Real-time RT-PCR of IFNgamma secretion-assay-enriched T-cells responding to the peptides, SALKLAIYKA and GLCPHCINVG, revealed a disproportionately high T-cell receptor Vbeta (TRBV) 11 expression in this population. Furthermore, dominant expression of type-1 (IFNgamma, IL2, IL27 and T-bet) and of cytotoxic T-cell markers (Perforin and Granzyme B) was found, whereas gene expression indicating type-2 (IL4, GATA3) and regulatory T-cells (FoxP3) was low. CONCLUSIONS: Our results indicate that B19V Ag-specific CD8(+) T-cells with effector function are involved in B19V associated DCMi. In particular, a dominant role of TRBV11 and type-1/CTL effector cells in the T-cell mediated antiviral immune response is suggested. The persistence of B19V in the endomyocardium is a likely antigen source for the maintenance of CD8(+) T-cell responses to the identified epitopes.

Item Type: Article
Keywords: Adult Amino Acid Sequence Base Sequence CD8-Positive T-Lymphocytes/*immunology Cardiomyopathies/*virology DNA Primers Flow Cytometry Humans Male Parvovirus B19, Human/*pathogenicity Receptors, Antigen, T-Cell, alpha-beta/*immunology Reverse Transcriptase Polymerase Chain Reaction Viral Nonstructural Proteins/*immunology
Schools and Departments: Brighton and Sussex Medical School > Clinical Medicine
Subjects: Q Science > QR Microbiology > QR0180 Immunology
Depositing User: Florian Kern
Date Deposited: 29 Oct 2012 11:27
Last Modified: 14 Mar 2017 02:08
URI: http://sro.sussex.ac.uk/id/eprint/41286

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