Human CD4+ T Helper Cell Responses after Tick-Borne Encephalitis Vaccination and Infection.
Tick-borne encephalitis virus (TBEV) is a human-pathogenic flavivirus that is endemic in large parts of Europe and Asia and causes severe neuroinvasive illness. A formalin-inactivated vaccine induces strong neutralizing antibody responses and confers protection from TBE disease. CD4+ T cell response...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4605778?pdf=render |
| _version_ | 1819268159542132736 |
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| author | Judith H Aberle Julia Schwaiger Stephan W Aberle Karin Stiasny Ondrej Scheinost Michael Kundi Vaclav Chmelik Franz X Heinz |
| author_facet | Judith H Aberle Julia Schwaiger Stephan W Aberle Karin Stiasny Ondrej Scheinost Michael Kundi Vaclav Chmelik Franz X Heinz |
| author_sort | Judith H Aberle |
| collection | DOAJ |
| description | Tick-borne encephalitis virus (TBEV) is a human-pathogenic flavivirus that is endemic in large parts of Europe and Asia and causes severe neuroinvasive illness. A formalin-inactivated vaccine induces strong neutralizing antibody responses and confers protection from TBE disease. CD4+ T cell responses are essential for neutralizing antibody production, but data on the functionalities of TBEV-specific CD4+ T cells in response to vaccination or infection are lacking. This study provides a comprehensive analysis of the cytokine patterns of CD4+ T cell responses in 20 humans after TBE vaccination in comparison to those in 18 patients with TBEV infection. Specifically, Th1-specific cytokines (IFN-γ, IL-2, TNF-α), CD40 ligand and the Th1 lineage-specifying transcription factor Tbet were determined upon stimulation with peptides covering the TBEV structural proteins contained in the vaccine (C-capsid, prM/M-membrane and E-envelope). We show that TBEV-specific CD4+ T cell responses are polyfunctional, but the cytokine patterns after vaccination differed from those after infection. TBE vaccine responses were characterized by lower IFN-γ responses and high proportions of TNF-α+IL-2+ cells. In vaccine-induced responses-consistent with the reduced IFN-γ expression patterns-less than 50% of TBEV peptides were detected by IFN-γ+ cells as compared to 96% detected by IL-2+ cells, indicating that the single use of IFN-γ as a read-out strongly underestimates the magnitude and breadth of such responses. The results provide important insights into the functionalities of CD4+ T cells that coordinate vaccine responses and have direct implications for future studies that address epitope specificity and breadth of these responses. |
| first_indexed | 2024-12-23T21:28:38Z |
| format | Article |
| id | doaj.art-51458fa43b874626beed0a74ed8bed95 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-23T21:28:38Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-51458fa43b874626beed0a74ed8bed952022-12-21T17:30:31ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-011010e014054510.1371/journal.pone.0140545Human CD4+ T Helper Cell Responses after Tick-Borne Encephalitis Vaccination and Infection.Judith H AberleJulia SchwaigerStephan W AberleKarin StiasnyOndrej ScheinostMichael KundiVaclav ChmelikFranz X HeinzTick-borne encephalitis virus (TBEV) is a human-pathogenic flavivirus that is endemic in large parts of Europe and Asia and causes severe neuroinvasive illness. A formalin-inactivated vaccine induces strong neutralizing antibody responses and confers protection from TBE disease. CD4+ T cell responses are essential for neutralizing antibody production, but data on the functionalities of TBEV-specific CD4+ T cells in response to vaccination or infection are lacking. This study provides a comprehensive analysis of the cytokine patterns of CD4+ T cell responses in 20 humans after TBE vaccination in comparison to those in 18 patients with TBEV infection. Specifically, Th1-specific cytokines (IFN-γ, IL-2, TNF-α), CD40 ligand and the Th1 lineage-specifying transcription factor Tbet were determined upon stimulation with peptides covering the TBEV structural proteins contained in the vaccine (C-capsid, prM/M-membrane and E-envelope). We show that TBEV-specific CD4+ T cell responses are polyfunctional, but the cytokine patterns after vaccination differed from those after infection. TBE vaccine responses were characterized by lower IFN-γ responses and high proportions of TNF-α+IL-2+ cells. In vaccine-induced responses-consistent with the reduced IFN-γ expression patterns-less than 50% of TBEV peptides were detected by IFN-γ+ cells as compared to 96% detected by IL-2+ cells, indicating that the single use of IFN-γ as a read-out strongly underestimates the magnitude and breadth of such responses. The results provide important insights into the functionalities of CD4+ T cells that coordinate vaccine responses and have direct implications for future studies that address epitope specificity and breadth of these responses.http://europepmc.org/articles/PMC4605778?pdf=render |
| spellingShingle | Judith H Aberle Julia Schwaiger Stephan W Aberle Karin Stiasny Ondrej Scheinost Michael Kundi Vaclav Chmelik Franz X Heinz Human CD4+ T Helper Cell Responses after Tick-Borne Encephalitis Vaccination and Infection. PLoS ONE |
| title | Human CD4+ T Helper Cell Responses after Tick-Borne Encephalitis Vaccination and Infection. |
| title_full | Human CD4+ T Helper Cell Responses after Tick-Borne Encephalitis Vaccination and Infection. |
| title_fullStr | Human CD4+ T Helper Cell Responses after Tick-Borne Encephalitis Vaccination and Infection. |
| title_full_unstemmed | Human CD4+ T Helper Cell Responses after Tick-Borne Encephalitis Vaccination and Infection. |
| title_short | Human CD4+ T Helper Cell Responses after Tick-Borne Encephalitis Vaccination and Infection. |
| title_sort | human cd4 t helper cell responses after tick borne encephalitis vaccination and infection |
| url | http://europepmc.org/articles/PMC4605778?pdf=render |
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