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 and Experimental Medicine
Subjects:	Q Science > QR Microbiology > QR0180 Immunology
Depositing User:	Florian Kern
Date Deposited:	29 Oct 2012 11:27
Last Modified:	02 Nov 2018 09:58
URI:	http://srodev.sussex.ac.uk/id/eprint/41286

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