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Heterologous T cell...
Heterologous T cells can help restore function in dysfunctional hepatitis C virus nonstructural 3/4A-specific T cells during therapeutic vaccination.
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Chen, Antony (författare)
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- Ahlén, Gustaf (författare)
- Karolinska Institutet
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- Brenndörfer, Erwin D (författare)
- Karolinska Institutet
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- Brass, Anette (författare)
- Karolinska Institutet
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- Holmström, Fredrik (författare)
- Karolinska Institutet
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- Chen, Margaret (författare)
- Karolinska Institutet
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- Söderholm, Jonas, 1978 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för infektionssjukdomar,Institute of Biomedicine, Department of Infectious Medicine
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Milich, David R (författare)
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- Frelin, Lars (författare)
- Karolinska Institutet
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- Sällberg, Matti (författare)
- Karolinska Institutet
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(creator_code:org_t)
- 2011-05-01
- 2011
- Engelska.
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Ingår i: Journal of immunology. - : The American Association of Immunologists. - 1550-6606 .- 0022-1767. ; 186:9, s. 5107-18
- Relaterad länk:
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http://www.jimmunol....
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https://gup.ub.gu.se...
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https://doi.org/10.4...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- The hepatitis C virus (HCV)-specific T cell response in patients with chronic HCV is dysfunctional. In this study, we aimed at restoring immunological function through therapeutic vaccination in a transgenic mouse model with impaired HCV-specific T cell responses due to a persistent presence of hepatic HCV nonstructural (NS)3/4A Ags. The HCV-specific T cells have an actively maintained dysfunction reflected in reduced frequency, impaired cytokine production, and impaired effector function in vivo, which can be partially restored by blocking regulatory T cells or programmed cell death ligand 1. We hypothesized that the impairment could be corrected by including sequences that created a normal priming environment by recruiting "healthy" heterologous T cells and by activating innate signaling. Endogenously expressed hepatitis B core Ag (HBcAg) can recruit heterologous T cells and activate TLR (TLR7) signaling. Hence, by combining HCV NS3/4A with different forms of HBcAg we found that heterologous sequences somewhat improved activation and expansion of NS3/4A-specific T cells in a wild-type host. Importantly, the signals provided by HBcAg effectively restored the activation of HCV-specific T cells in a tolerant NS3/4A-transgenic mouse model. The adjuvant effect could also be transferred to the priming of dysfunctional HLA-A2-restricted NS3-specific T cells in vivo. Thus, recruiting healthy heterologous T cells to the site of priming may also help restore HCV-specific responses present in a chronically infected host.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Infectious Medicine (hsv//eng)
Nyckelord
- Animals
- Animals
- Genetically Modified
- Antigens
- Viral
- immunology
- therapeutic use
- Blotting
- Western
- Cell Line
- Tumor
- Disease Models
- Animal
- Enzyme-Linked Immunosorbent Assay
- Hepacivirus
- immunology
- Hepatitis B Core Antigens
- immunology
- therapeutic use
- Hepatitis C
- Chronic
- immunology
- therapy
- Humans
- Immunoprecipitation
- Lymphocyte Activation
- immunology
- Mice
- Mice
- Inbred BALB C
- Mice
- Inbred C57BL
- Mice
- Transgenic
- T-Lymphocytes
- immunology
- Vaccination
- methods
- Viral Hepatitis Vaccines
- immunology
- Viral Nonstructural Proteins
- immunology
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
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Chen, Antony
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Ahlén, Gustaf
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Brenndörfer, Erw ...
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Brass, Anette
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Holmström, Fredr ...
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Chen, Margaret
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visa fler...
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Söderholm, Jonas ...
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Milich, David R
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Frelin, Lars
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Sällberg, Matti
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Immunologi inom ...
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Infektionsmedici ...
- Artiklar i publikationen
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Journal of immun ...
- Av lärosätet
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Göteborgs universitet
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Karolinska Institutet