NS1 Specific CD8(+) T-Cells with Effector Function and TRBV11 Dominance in a Patient with Parvovirus B19 Associated Inflammatory Cardiomyopathy
| Autor: | Michael Hummel, Rudolf Volkmer, Florian Kern, Andrea Block, G. Brestrich, Katja Kotsch, Maria Rohde, Uwe Kühl, Heinz-Peter Schultheiss, Michel Noutsias, Katrin Klippert, Mathias Streitz, Dirk Lassner, Bernhard Ay, Hans-Dieter Volk |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Adult
Male Receptors Antigen T-Cell alpha-beta lcsh:Medicine CD8-Positive T-Lymphocytes Viral Nonstructural Proteins Biology Q1 Epitope QH301 Immune system Antigen Immunology/Immunity to Infections Parvovirus B19 Human Humans Cytotoxic T cell Amino Acid Sequence lcsh:Science DNA Primers Multidisciplinary Base Sequence Reverse Transcriptase Polymerase Chain Reaction lcsh:R FOXP3 Flow Cytometry Virology Granzyme B Immunology QR180 lcsh:Q Cardiovascular Disorders/Myopathies Virology/Host Antiviral Responses Cardiomyopathies Viral load CD8 Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 3, Iss 6, p e2361 (2008) |
| ISSN: | 1932-6203 |
| Popis: | 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. \ud \ud Methodology and Principal Findings: An exceptionally high B19V viral load in EMBs (115,091 viral copies/mg 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-amico-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 IFN gamma 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 (IFN gamma, IL2, IL27 and Tbet) 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. \ud \ud 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|