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


RESULTS
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.
Institute of Medical Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Mathias
M
Streitz
Michel
M
Noutsias
Rudolf
R
Volkmer
Maria
M
Rohde
Gordon
G
Brestrich
Andrea
A
Block
Katrin
K
Klippert
Katja
K
Kotsch
Bernhard
B
Ay
Michael
M
Hummel
Uwe
U
Kühl
Dirk
D
Lassner
Heinz-Peter
HP
Schultheiss
Hans-Dieter
HD
Volk
Florian
F
Kern
D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D009202:Cardiomyopathies / Q000821:virology*; D017931:DNA Primers; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D016732:Parvovirus B19, Human / Q000472:pathogenicity*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017361:Viral Nonstructural Proteins / Q000276:immunology*
D017931:DNA Primers; C106202:NS1 protein, parvovirus; D016693:Receptors, Antigen, T-Cell, alpha-beta; D017361:Viral Nonstructural Proteins