Partial depletion of regulatory T cells does not influence the inflammation caused by high dose hemi-body irradiation.

There is clinical interest in the modulation of regulatory T cells for cancer therapy. The safety of these therapies in combination with conventional anti-cancer therapies, including radiation therapy, can be studied in animal models. The effects of partial depletion of regulatory T (Treg) cells wit...

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Autores principales:	Shihong Ma, James A Richardson, Andrew Bitmansour, Timothy D Solberg, Rajesh Pidikiti, Kwang Song, Strahinja Stojadinovic, Ellen S Vitetta, Jeffrey J Meyer
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e69132d8d7e0470d968463490df32828
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spelling	oai:doaj.org-article:e69132d8d7e0470d968463490df328282021-11-18T07:57:59ZPartial depletion of regulatory T cells does not influence the inflammation caused by high dose hemi-body irradiation.1932-620310.1371/journal.pone.0056607https://doaj.org/article/e69132d8d7e0470d968463490df328282013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23409194/?tool=EBIhttps://doaj.org/toc/1932-6203There is clinical interest in the modulation of regulatory T cells for cancer therapy. The safety of these therapies in combination with conventional anti-cancer therapies, including radiation therapy, can be studied in animal models. The effects of partial depletion of regulatory T (Treg) cells with an anti-CD25 antibody in conjunction with ionizing radiation on inflammation and tissue injury were analyzed in C57BL/6 mice. An anti-CD25 antibody (PC61) was administered 3 days prior to 13 Gy lower-half hemi-body irradiation (HBI). The blood, spleen, mesenteric lymph nodes (mLNs) and inguinal lymph nodes (iLNs) were harvested at various times thereafter. Alterations in the proportion of leukocyte subsets including CD4(+) T cells, CD8(+) T cells, Treg cells, B cells, NK cells, NK1.1(+) T cells, macrophages and granulocytes were analyzed by FACS. The lungs, liver, pancreas, stomach, jejunum, duodenum, ileum, colon and kidney were harvested and studied by H&E staining. Expression of inflammatory mediators in plasma and tissue were investigated by ELISA. HBI significantly decreased the leukocyte pool though the various leukocyte subsets had different sensitivities to HBI. The administration of PC61 significantly decreased the proportion of Treg cells in spleen, iLN, mLN and blood (reduction of approximately 60%). Irradiation significantly increased the proportion of Treg cells in the spleen, iLN and mLN. HBI induced a systemic inflammatory reaction as demonstrated by increased plasma levels of IL-6, KC/CXCL1 and circulating granulocytes in the blood. Neutrophils also infiltrated the small bowel. The same general patterns were observed whether or not Treg cells were partially depleted with PC61 prior to HBI. These data demonstrate that partial depletion of Treg cells in these mice does not influence HBI-induced inflammatory response and tissue injury, and that combining anti-CD25 therapy with radiation may be safe and well tolerated in a clinical setting.Shihong MaJames A RichardsonAndrew BitmansourTimothy D SolbergRajesh PidikitiKwang SongStrahinja StojadinovicEllen S VitettaJeffrey J MeyerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 2, p e56607 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shihong Ma James A Richardson Andrew Bitmansour Timothy D Solberg Rajesh Pidikiti Kwang Song Strahinja Stojadinovic Ellen S Vitetta Jeffrey J Meyer Partial depletion of regulatory T cells does not influence the inflammation caused by high dose hemi-body irradiation.
description	There is clinical interest in the modulation of regulatory T cells for cancer therapy. The safety of these therapies in combination with conventional anti-cancer therapies, including radiation therapy, can be studied in animal models. The effects of partial depletion of regulatory T (Treg) cells with an anti-CD25 antibody in conjunction with ionizing radiation on inflammation and tissue injury were analyzed in C57BL/6 mice. An anti-CD25 antibody (PC61) was administered 3 days prior to 13 Gy lower-half hemi-body irradiation (HBI). The blood, spleen, mesenteric lymph nodes (mLNs) and inguinal lymph nodes (iLNs) were harvested at various times thereafter. Alterations in the proportion of leukocyte subsets including CD4(+) T cells, CD8(+) T cells, Treg cells, B cells, NK cells, NK1.1(+) T cells, macrophages and granulocytes were analyzed by FACS. The lungs, liver, pancreas, stomach, jejunum, duodenum, ileum, colon and kidney were harvested and studied by H&E staining. Expression of inflammatory mediators in plasma and tissue were investigated by ELISA. HBI significantly decreased the leukocyte pool though the various leukocyte subsets had different sensitivities to HBI. The administration of PC61 significantly decreased the proportion of Treg cells in spleen, iLN, mLN and blood (reduction of approximately 60%). Irradiation significantly increased the proportion of Treg cells in the spleen, iLN and mLN. HBI induced a systemic inflammatory reaction as demonstrated by increased plasma levels of IL-6, KC/CXCL1 and circulating granulocytes in the blood. Neutrophils also infiltrated the small bowel. The same general patterns were observed whether or not Treg cells were partially depleted with PC61 prior to HBI. These data demonstrate that partial depletion of Treg cells in these mice does not influence HBI-induced inflammatory response and tissue injury, and that combining anti-CD25 therapy with radiation may be safe and well tolerated in a clinical setting.
format	article
author	Shihong Ma James A Richardson Andrew Bitmansour Timothy D Solberg Rajesh Pidikiti Kwang Song Strahinja Stojadinovic Ellen S Vitetta Jeffrey J Meyer
author_facet	Shihong Ma James A Richardson Andrew Bitmansour Timothy D Solberg Rajesh Pidikiti Kwang Song Strahinja Stojadinovic Ellen S Vitetta Jeffrey J Meyer
author_sort	Shihong Ma
title	Partial depletion of regulatory T cells does not influence the inflammation caused by high dose hemi-body irradiation.
title_short	Partial depletion of regulatory T cells does not influence the inflammation caused by high dose hemi-body irradiation.
title_full	Partial depletion of regulatory T cells does not influence the inflammation caused by high dose hemi-body irradiation.
title_fullStr	Partial depletion of regulatory T cells does not influence the inflammation caused by high dose hemi-body irradiation.
title_full_unstemmed	Partial depletion of regulatory T cells does not influence the inflammation caused by high dose hemi-body irradiation.
title_sort	partial depletion of regulatory t cells does not influence the inflammation caused by high dose hemi-body irradiation.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/e69132d8d7e0470d968463490df32828
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Partial depletion of regulatory T cells does not influence the inflammation caused by high dose hemi-body irradiation.

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