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. METHODOLOGY A...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2008-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2394660?pdf=render |
| _version_ | 1828308483667132416 |
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| author | Mathias Streitz Michel Noutsias Rudolf Volkmer Maria Rohde Gordon Brestrich Andrea Block Katrin Klippert Katja Kotsch Bernhard Ay Michael Hummel Uwe Kühl Dirk Lassner Heinz-Peter Schultheiss Hans-Dieter Volk Florian Kern |
| author_facet | Mathias Streitz Michel Noutsias Rudolf Volkmer Maria Rohde Gordon Brestrich Andrea Block Katrin Klippert Katja Kotsch Bernhard Ay Michael Hummel Uwe Kühl Dirk Lassner Heinz-Peter Schultheiss Hans-Dieter Volk Florian Kern |
| author_sort | Mathias Streitz |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T15:14:03Z |
| format | Article |
| id | doaj.art-076efbbdd8074bf895e74abf25c7b55e |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T15:14:03Z |
| publishDate | 2008-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-076efbbdd8074bf895e74abf25c7b55e2022-12-22T02:41:54ZengPublic Library of Science (PLoS)PLoS ONE1932-62032008-01-0136e236110.1371/journal.pone.0002361NS1 specific CD8+ T-cells with effector function and TRBV11 dominance in a patient with parvovirus B19 associated inflammatory cardiomyopathy.Mathias StreitzMichel NoutsiasRudolf VolkmerMaria RohdeGordon BrestrichAndrea BlockKatrin KlippertKatja KotschBernhard AyMichael HummelUwe KühlDirk LassnerHeinz-Peter SchultheissHans-Dieter VolkFlorian KernBACKGROUND: 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.http://europepmc.org/articles/PMC2394660?pdf=render |
| spellingShingle | Mathias Streitz Michel Noutsias Rudolf Volkmer Maria Rohde Gordon Brestrich Andrea Block Katrin Klippert Katja Kotsch Bernhard Ay Michael Hummel Uwe Kühl Dirk Lassner Heinz-Peter Schultheiss Hans-Dieter Volk Florian Kern NS1 specific CD8+ T-cells with effector function and TRBV11 dominance in a patient with parvovirus B19 associated inflammatory cardiomyopathy. PLoS ONE |
| title | NS1 specific CD8+ T-cells with effector function and TRBV11 dominance in a patient with parvovirus B19 associated inflammatory cardiomyopathy. |
| title_full | NS1 specific CD8+ T-cells with effector function and TRBV11 dominance in a patient with parvovirus B19 associated inflammatory cardiomyopathy. |
| title_fullStr | NS1 specific CD8+ T-cells with effector function and TRBV11 dominance in a patient with parvovirus B19 associated inflammatory cardiomyopathy. |
| title_full_unstemmed | NS1 specific CD8+ T-cells with effector function and TRBV11 dominance in a patient with parvovirus B19 associated inflammatory cardiomyopathy. |
| title_short | NS1 specific CD8+ T-cells with effector function and TRBV11 dominance in a patient with parvovirus B19 associated inflammatory cardiomyopathy. |
| title_sort | ns1 specific cd8 t cells with effector function and trbv11 dominance in a patient with parvovirus b19 associated inflammatory cardiomyopathy |
| url | http://europepmc.org/articles/PMC2394660?pdf=render |
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