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Leishmania Specific CD4 T Cells Release IFNγ That Limits Parasite Replication in Patients with Visceral Leishmaniasis

Visceral leishmaniasis (VL) is associated with increased circulating levels of multiple pro-inflammatory cytokines and chemokines, including IL-12, IFNγ, and TNFα, and elevated expression of IFNγ mRNA in lesional tissue such as the spleen and bone marrow. However, an immunological feature of VL pati...

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Autores principales: Kumar, Rajiv, Singh, Neetu, Gautam, Shalini, Singh, Om Prakash, Gidwani, Kamlesh, Rai, Madhukar, Sacks, David, Sundar, Shyam, Nylén, Susanne
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4183461/
https://www.ncbi.nlm.nih.gov/pubmed/25275531
http://dx.doi.org/10.1371/journal.pntd.0003198
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author Kumar, Rajiv
Singh, Neetu
Gautam, Shalini
Singh, Om Prakash
Gidwani, Kamlesh
Rai, Madhukar
Sacks, David
Sundar, Shyam
Nylén, Susanne
author_facet Kumar, Rajiv
Singh, Neetu
Gautam, Shalini
Singh, Om Prakash
Gidwani, Kamlesh
Rai, Madhukar
Sacks, David
Sundar, Shyam
Nylén, Susanne
author_sort Kumar, Rajiv
collection PubMed
description Visceral leishmaniasis (VL) is associated with increased circulating levels of multiple pro-inflammatory cytokines and chemokines, including IL-12, IFNγ, and TNFα, and elevated expression of IFNγ mRNA in lesional tissue such as the spleen and bone marrow. However, an immunological feature of VL patients is that their peripheral blood mononuclear cells (PBMCs) typically fail to respond to stimulation with leishmanial antigen. Unexpectedly, it was recently shown that Leishmania specific IFNγ, can readily be detected when a whole blood stimulation assay (WBA) is used. We sought to define the conditions that permit whole blood cells to respond to antigen stimulation, and clarify the biological role of the IFNγ found to be released by cells from VL patients. CD4+ T cells were found to be crucial for and the main source of the IFNγ production in Leishmania stimulated whole blood (WB) cultures. Complement, antibodies and red blood cells present in whole blood do not play a significant role in the IFNγ response. The IFNγ production was reduced by blockade of human leukocyte antigen (HLA)-DR, indicating that the response to leishmanial antigens observed in WB of active VL patients is a classical HLA- T cell receptor (TCR) driven reaction. Most importantly, blockade of IFNγ in ex-vivo splenic aspirate cultures demonstrated that despite the progressive nature of their disease, the endogenous IFNγ produced in patients with active VL serves to limit parasite growth.
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spelling pubmed-41834612014-10-07 Leishmania Specific CD4 T Cells Release IFNγ That Limits Parasite Replication in Patients with Visceral Leishmaniasis Kumar, Rajiv Singh, Neetu Gautam, Shalini Singh, Om Prakash Gidwani, Kamlesh Rai, Madhukar Sacks, David Sundar, Shyam Nylén, Susanne PLoS Negl Trop Dis Research Article Visceral leishmaniasis (VL) is associated with increased circulating levels of multiple pro-inflammatory cytokines and chemokines, including IL-12, IFNγ, and TNFα, and elevated expression of IFNγ mRNA in lesional tissue such as the spleen and bone marrow. However, an immunological feature of VL patients is that their peripheral blood mononuclear cells (PBMCs) typically fail to respond to stimulation with leishmanial antigen. Unexpectedly, it was recently shown that Leishmania specific IFNγ, can readily be detected when a whole blood stimulation assay (WBA) is used. We sought to define the conditions that permit whole blood cells to respond to antigen stimulation, and clarify the biological role of the IFNγ found to be released by cells from VL patients. CD4+ T cells were found to be crucial for and the main source of the IFNγ production in Leishmania stimulated whole blood (WB) cultures. Complement, antibodies and red blood cells present in whole blood do not play a significant role in the IFNγ response. The IFNγ production was reduced by blockade of human leukocyte antigen (HLA)-DR, indicating that the response to leishmanial antigens observed in WB of active VL patients is a classical HLA- T cell receptor (TCR) driven reaction. Most importantly, blockade of IFNγ in ex-vivo splenic aspirate cultures demonstrated that despite the progressive nature of their disease, the endogenous IFNγ produced in patients with active VL serves to limit parasite growth. Public Library of Science 2014-10-02 /pmc/articles/PMC4183461/ /pubmed/25275531 http://dx.doi.org/10.1371/journal.pntd.0003198 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
spellingShingle Research Article
Kumar, Rajiv
Singh, Neetu
Gautam, Shalini
Singh, Om Prakash
Gidwani, Kamlesh
Rai, Madhukar
Sacks, David
Sundar, Shyam
Nylén, Susanne
Leishmania Specific CD4 T Cells Release IFNγ That Limits Parasite Replication in Patients with Visceral Leishmaniasis
title Leishmania Specific CD4 T Cells Release IFNγ That Limits Parasite Replication in Patients with Visceral Leishmaniasis
title_full Leishmania Specific CD4 T Cells Release IFNγ That Limits Parasite Replication in Patients with Visceral Leishmaniasis
title_fullStr Leishmania Specific CD4 T Cells Release IFNγ That Limits Parasite Replication in Patients with Visceral Leishmaniasis
title_full_unstemmed Leishmania Specific CD4 T Cells Release IFNγ That Limits Parasite Replication in Patients with Visceral Leishmaniasis
title_short Leishmania Specific CD4 T Cells Release IFNγ That Limits Parasite Replication in Patients with Visceral Leishmaniasis
title_sort leishmania specific cd4 t cells release ifnγ that limits parasite replication in patients with visceral leishmaniasis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4183461/
https://www.ncbi.nlm.nih.gov/pubmed/25275531
http://dx.doi.org/10.1371/journal.pntd.0003198
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