Natural CD4+ T-cell responses against indoleamine 2,3-dioxygenase.

<h4>Background</h4>The enzyme indoleamine 2,3-dioxygenase (IDO) contributes to immune tolerance in a variety of settings. In cancer IDO is expressed within the tumor itself as well as in antigen-presenting cells in tumor-draining lymph nodes, where it endorses the establishment of periph...

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Autores principales:	Shamaila Munir, Stine Kiaer Larsen, Trine Zeeberg Iversen, Marco Donia, Tobias Wirenfeldt Klausen, Inge Marie Svane, Per Thor Straten, Mads Hald Andersen
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/43c912dc0ef8454d91ae6843fa1218ca
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spelling	oai:doaj.org-article:43c912dc0ef8454d91ae6843fa1218ca2021-11-18T07:21:19ZNatural CD4+ T-cell responses against indoleamine 2,3-dioxygenase.1932-620310.1371/journal.pone.0034568https://doaj.org/article/43c912dc0ef8454d91ae6843fa1218ca2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22539948/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>The enzyme indoleamine 2,3-dioxygenase (IDO) contributes to immune tolerance in a variety of settings. In cancer IDO is expressed within the tumor itself as well as in antigen-presenting cells in tumor-draining lymph nodes, where it endorses the establishment of peripheral immune tolerance to tumor antigens. Recently, we described cytotoxic CD8(+) T-cell reactivity towards IDO-derived peptides.<h4>Methods and findings</h4>In the present study, we show that CD4(+) helper T cells additionally spontaneously recognize IDO. Hence, we scrutinized the vicinity of the previously described HLA-A*0201-restricted IDO-epitope for CD4(+) T-cell epitopes. We demonstrated the presence of naturally occurring IDO-specific CD4(+) T cells in cancer patients and to a lesser extent in healthy donors by cytokine release ELISPOT. IDO-reactive CD4(+) T cells released IFN-γ, TNF-α, as well as IL-17. We confirm HLA class II-restriction by the addition of HLA class II specific blocking antibodies. In addition, we detected a trend between class I- and class II-restricted IDO responses and detected an association between IDO-specific CD4(+) T cells and CD8(+) CMV-responses. Finally, we could detect IL-10 releasing IDO-reactive CD4(+) T cells.<h4>Conclusion</h4>IDO is spontaneously recognized by HLA class II-restricted, CD4(+) T cells in cancer patients and in healthy individuals. IDO-specific T cells may participate in immune-regulatory networks where the activation of pro-inflammatory IDO-specific CD4(+) responses may well overcome or delay the immune suppressive actions of the IDO-protein, which are otherwise a consequence of the early expression of IDO in maturing antigen presenting cells. In contrast, IDO-specific regulatory T cells may enhance IDO-mediated immune suppression.Shamaila MunirStine Kiaer LarsenTrine Zeeberg IversenMarco DoniaTobias Wirenfeldt KlausenInge Marie SvanePer Thor StratenMads Hald AndersenPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 4, p e34568 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shamaila Munir Stine Kiaer Larsen Trine Zeeberg Iversen Marco Donia Tobias Wirenfeldt Klausen Inge Marie Svane Per Thor Straten Mads Hald Andersen Natural CD4+ T-cell responses against indoleamine 2,3-dioxygenase.
description	<h4>Background</h4>The enzyme indoleamine 2,3-dioxygenase (IDO) contributes to immune tolerance in a variety of settings. In cancer IDO is expressed within the tumor itself as well as in antigen-presenting cells in tumor-draining lymph nodes, where it endorses the establishment of peripheral immune tolerance to tumor antigens. Recently, we described cytotoxic CD8(+) T-cell reactivity towards IDO-derived peptides.<h4>Methods and findings</h4>In the present study, we show that CD4(+) helper T cells additionally spontaneously recognize IDO. Hence, we scrutinized the vicinity of the previously described HLA-A*0201-restricted IDO-epitope for CD4(+) T-cell epitopes. We demonstrated the presence of naturally occurring IDO-specific CD4(+) T cells in cancer patients and to a lesser extent in healthy donors by cytokine release ELISPOT. IDO-reactive CD4(+) T cells released IFN-γ, TNF-α, as well as IL-17. We confirm HLA class II-restriction by the addition of HLA class II specific blocking antibodies. In addition, we detected a trend between class I- and class II-restricted IDO responses and detected an association between IDO-specific CD4(+) T cells and CD8(+) CMV-responses. Finally, we could detect IL-10 releasing IDO-reactive CD4(+) T cells.<h4>Conclusion</h4>IDO is spontaneously recognized by HLA class II-restricted, CD4(+) T cells in cancer patients and in healthy individuals. IDO-specific T cells may participate in immune-regulatory networks where the activation of pro-inflammatory IDO-specific CD4(+) responses may well overcome or delay the immune suppressive actions of the IDO-protein, which are otherwise a consequence of the early expression of IDO in maturing antigen presenting cells. In contrast, IDO-specific regulatory T cells may enhance IDO-mediated immune suppression.
format	article
author	Shamaila Munir Stine Kiaer Larsen Trine Zeeberg Iversen Marco Donia Tobias Wirenfeldt Klausen Inge Marie Svane Per Thor Straten Mads Hald Andersen
author_facet	Shamaila Munir Stine Kiaer Larsen Trine Zeeberg Iversen Marco Donia Tobias Wirenfeldt Klausen Inge Marie Svane Per Thor Straten Mads Hald Andersen
author_sort	Shamaila Munir
title	Natural CD4+ T-cell responses against indoleamine 2,3-dioxygenase.
title_short	Natural CD4+ T-cell responses against indoleamine 2,3-dioxygenase.
title_full	Natural CD4+ T-cell responses against indoleamine 2,3-dioxygenase.
title_fullStr	Natural CD4+ T-cell responses against indoleamine 2,3-dioxygenase.
title_full_unstemmed	Natural CD4+ T-cell responses against indoleamine 2,3-dioxygenase.
title_sort	natural cd4+ t-cell responses against indoleamine 2,3-dioxygenase.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/43c912dc0ef8454d91ae6843fa1218ca
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Natural CD4+ T-cell responses against indoleamine 2,3-dioxygenase.

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