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Antigen-Specific CD4 T Cells Are Induced after Intravesical BCG-Instillation Therapy in Patients with Bladder Cancer and Show Similar Cytokine Profiles as in Active Tuberculosis
Specific T cell immunity in patients with active tuberculosis is associated with a decrease in multifunctionality. However, it is unknown whether cytokine profiles differ in patients with primary infection and those with prior contact. We therefore used intravesical immunotherapy with attenuated liv...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3770812/ https://www.ncbi.nlm.nih.gov/pubmed/24039703 http://dx.doi.org/10.1371/journal.pone.0069892 |
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author | Elsäßer, Julia Janssen, Martin W. Becker, Frank Suttmann, Henrik Schmitt, Kai Sester, Urban Stöckle, Michael Sester, Martina |
author_facet | Elsäßer, Julia Janssen, Martin W. Becker, Frank Suttmann, Henrik Schmitt, Kai Sester, Urban Stöckle, Michael Sester, Martina |
author_sort | Elsäßer, Julia |
collection | PubMed |
description | Specific T cell immunity in patients with active tuberculosis is associated with a decrease in multifunctionality. However, it is unknown whether cytokine profiles differ in patients with primary infection and those with prior contact. We therefore used intravesical immunotherapy with attenuated live Bacille Calmette–Guérin (BCG) in patients with urothelial carcinoma as a model to characterise the induction of systemic immunity towards purified protein derivate (PPD) and to study whether cytokine profiles differ depending on pre-existing immunity. Eighteen patients with non-muscle invasive bladder cancer were recruited during the BCG-induction course. Fifty-four healthy individuals served as controls. Interferon (IFN)-γ and interleukin (IL)-2 producing PPD-specific CD4 T cells were analysed longitudinally before each instillation using a rapid flow-cytometric whole blood immunoassay. Baseline levels of IFN-γ producing PPD-specific T cells were comparable to controls. T cells showed a 5-fold increase to 0.23% by week 2/3, and further increased 8-fold by week 4/5 (to 0.42%, p=0.0007). Systemic immunity was induced in all patients, although the increase was less pronounced in patients with pre-existing immunity. As in active TB, cytokine profiling during therapy revealed a lower percentage of multifunctional IFN-γ/IL-2 double-positive T cells compared to controls (60.2% vs. 71.9%, p=0.0003). Of note, when comparing patients with and without pre-existing immunity, cytokine profiles in patients with primary immunity were shifted towards IL-2 single producing T cells (p=0.02), whereas those in patients with pre-existing immunity were shifted towards IFN-γ single-positivity (p=0.01). In conclusion, systemic T cell responses were induced after BCG-therapy, and their kinetics and cytokine profile depended on pre-existing immunity. Decreased functionality is a typical feature of specific immunity in both patients with active tuberculosis and BCG-therapy. Among patients with active infection, a shift towards IL-2 or IFN-γ single-positive cells may allow distinction between patients with primary infection and cases with boosted immunity after prior contact, respectively. |
format | Online Article Text |
id | pubmed-3770812 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-37708122013-09-13 Antigen-Specific CD4 T Cells Are Induced after Intravesical BCG-Instillation Therapy in Patients with Bladder Cancer and Show Similar Cytokine Profiles as in Active Tuberculosis Elsäßer, Julia Janssen, Martin W. Becker, Frank Suttmann, Henrik Schmitt, Kai Sester, Urban Stöckle, Michael Sester, Martina PLoS One Research Article Specific T cell immunity in patients with active tuberculosis is associated with a decrease in multifunctionality. However, it is unknown whether cytokine profiles differ in patients with primary infection and those with prior contact. We therefore used intravesical immunotherapy with attenuated live Bacille Calmette–Guérin (BCG) in patients with urothelial carcinoma as a model to characterise the induction of systemic immunity towards purified protein derivate (PPD) and to study whether cytokine profiles differ depending on pre-existing immunity. Eighteen patients with non-muscle invasive bladder cancer were recruited during the BCG-induction course. Fifty-four healthy individuals served as controls. Interferon (IFN)-γ and interleukin (IL)-2 producing PPD-specific CD4 T cells were analysed longitudinally before each instillation using a rapid flow-cytometric whole blood immunoassay. Baseline levels of IFN-γ producing PPD-specific T cells were comparable to controls. T cells showed a 5-fold increase to 0.23% by week 2/3, and further increased 8-fold by week 4/5 (to 0.42%, p=0.0007). Systemic immunity was induced in all patients, although the increase was less pronounced in patients with pre-existing immunity. As in active TB, cytokine profiling during therapy revealed a lower percentage of multifunctional IFN-γ/IL-2 double-positive T cells compared to controls (60.2% vs. 71.9%, p=0.0003). Of note, when comparing patients with and without pre-existing immunity, cytokine profiles in patients with primary immunity were shifted towards IL-2 single producing T cells (p=0.02), whereas those in patients with pre-existing immunity were shifted towards IFN-γ single-positivity (p=0.01). In conclusion, systemic T cell responses were induced after BCG-therapy, and their kinetics and cytokine profile depended on pre-existing immunity. Decreased functionality is a typical feature of specific immunity in both patients with active tuberculosis and BCG-therapy. Among patients with active infection, a shift towards IL-2 or IFN-γ single-positive cells may allow distinction between patients with primary infection and cases with boosted immunity after prior contact, respectively. Public Library of Science 2013-09-11 /pmc/articles/PMC3770812/ /pubmed/24039703 http://dx.doi.org/10.1371/journal.pone.0069892 Text en © 2013 Elsäßer et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Elsäßer, Julia Janssen, Martin W. Becker, Frank Suttmann, Henrik Schmitt, Kai Sester, Urban Stöckle, Michael Sester, Martina Antigen-Specific CD4 T Cells Are Induced after Intravesical BCG-Instillation Therapy in Patients with Bladder Cancer and Show Similar Cytokine Profiles as in Active Tuberculosis |
title | Antigen-Specific CD4 T Cells Are Induced after Intravesical BCG-Instillation Therapy in Patients with Bladder Cancer and Show Similar Cytokine Profiles as in Active Tuberculosis |
title_full | Antigen-Specific CD4 T Cells Are Induced after Intravesical BCG-Instillation Therapy in Patients with Bladder Cancer and Show Similar Cytokine Profiles as in Active Tuberculosis |
title_fullStr | Antigen-Specific CD4 T Cells Are Induced after Intravesical BCG-Instillation Therapy in Patients with Bladder Cancer and Show Similar Cytokine Profiles as in Active Tuberculosis |
title_full_unstemmed | Antigen-Specific CD4 T Cells Are Induced after Intravesical BCG-Instillation Therapy in Patients with Bladder Cancer and Show Similar Cytokine Profiles as in Active Tuberculosis |
title_short | Antigen-Specific CD4 T Cells Are Induced after Intravesical BCG-Instillation Therapy in Patients with Bladder Cancer and Show Similar Cytokine Profiles as in Active Tuberculosis |
title_sort | antigen-specific cd4 t cells are induced after intravesical bcg-instillation therapy in patients with bladder cancer and show similar cytokine profiles as in active tuberculosis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3770812/ https://www.ncbi.nlm.nih.gov/pubmed/24039703 http://dx.doi.org/10.1371/journal.pone.0069892 |
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