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Preventive Anti-CD2 Treatment does not Impair Parasite Control in a Murine Toxoplasmosis Model

Targeting human CD2 with the monoclonal antibody (mAb) CB.219 reduces intestinal inflammation in a colitis model where T cells carry human CD2. Here, we asked whether this mAb has adverse effects on infection control. Mice expressing human CD2 on T cells (huCD2tg) were orally infected with Toxoplasm...

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Autores principales: Erben, U., Pawlowski, N. N., Heimesaat, M. M., Loddenkemper, C., Doerfel, K., Spieckermann, S., Siegmund, B., Kühl, A. A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Akadémiai Kiadó 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4681358/
https://www.ncbi.nlm.nih.gov/pubmed/26716019
http://dx.doi.org/10.1556/1886.2015.00040
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author Erben, U.
Pawlowski, N. N.
Heimesaat, M. M.
Loddenkemper, C.
Doerfel, K.
Spieckermann, S.
Siegmund, B.
Kühl, A. A.
author_facet Erben, U.
Pawlowski, N. N.
Heimesaat, M. M.
Loddenkemper, C.
Doerfel, K.
Spieckermann, S.
Siegmund, B.
Kühl, A. A.
author_sort Erben, U.
collection PubMed
description Targeting human CD2 with the monoclonal antibody (mAb) CB.219 reduces intestinal inflammation in a colitis model where T cells carry human CD2. Here, we asked whether this mAb has adverse effects on infection control. Mice expressing human CD2 on T cells (huCD2tg) were orally infected with Toxoplasma (T.) gondii and treated with the human CD2-specific mAb CB.219 in a preventive setting. The intestinal T. gondii loads in CB.219 treated mice did not differ from the control group. Histologically, huCD2tg mice showed moderate ileal inflammation that did not change with CB.219 treatment. In the ileum, CB.219 treatment reduced the protein levels of interferon-γ, transforming growth factor β and interleukin-6, whereas interleukin-18 mRNA was slightly increased. The infiltration of neutrophils, macrophages, and T cells into the ileum was unaffected by CB.219 treatment. However, CB.219 treatment decreased the numbers of forkhead box P3(+) regulatory T cells (Treg) in ileum and liver of huCD2tg mice. This was confirmed in vitro using human peripheral blood mononuclear cells. Taken together, targeting CD2(+) T cells by the human CD2 mAb CB.219 does not prevent beneficial immune reactions necessary for pathogen control. Further experiments will address gut specificity, underlying mechanisms, and general applicability of CB.219 treatment.
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spelling pubmed-46813582015-12-29 Preventive Anti-CD2 Treatment does not Impair Parasite Control in a Murine Toxoplasmosis Model Erben, U. Pawlowski, N. N. Heimesaat, M. M. Loddenkemper, C. Doerfel, K. Spieckermann, S. Siegmund, B. Kühl, A. A. Eur J Microbiol Immunol (Bp) Original Article Targeting human CD2 with the monoclonal antibody (mAb) CB.219 reduces intestinal inflammation in a colitis model where T cells carry human CD2. Here, we asked whether this mAb has adverse effects on infection control. Mice expressing human CD2 on T cells (huCD2tg) were orally infected with Toxoplasma (T.) gondii and treated with the human CD2-specific mAb CB.219 in a preventive setting. The intestinal T. gondii loads in CB.219 treated mice did not differ from the control group. Histologically, huCD2tg mice showed moderate ileal inflammation that did not change with CB.219 treatment. In the ileum, CB.219 treatment reduced the protein levels of interferon-γ, transforming growth factor β and interleukin-6, whereas interleukin-18 mRNA was slightly increased. The infiltration of neutrophils, macrophages, and T cells into the ileum was unaffected by CB.219 treatment. However, CB.219 treatment decreased the numbers of forkhead box P3(+) regulatory T cells (Treg) in ileum and liver of huCD2tg mice. This was confirmed in vitro using human peripheral blood mononuclear cells. Taken together, targeting CD2(+) T cells by the human CD2 mAb CB.219 does not prevent beneficial immune reactions necessary for pathogen control. Further experiments will address gut specificity, underlying mechanisms, and general applicability of CB.219 treatment. Akadémiai Kiadó 2015-11-12 /pmc/articles/PMC4681358/ /pubmed/26716019 http://dx.doi.org/10.1556/1886.2015.00040 Text en © 2015, The Author(s) http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Erben, U.
Pawlowski, N. N.
Heimesaat, M. M.
Loddenkemper, C.
Doerfel, K.
Spieckermann, S.
Siegmund, B.
Kühl, A. A.
Preventive Anti-CD2 Treatment does not Impair Parasite Control in a Murine Toxoplasmosis Model
title Preventive Anti-CD2 Treatment does not Impair Parasite Control in a Murine Toxoplasmosis Model
title_full Preventive Anti-CD2 Treatment does not Impair Parasite Control in a Murine Toxoplasmosis Model
title_fullStr Preventive Anti-CD2 Treatment does not Impair Parasite Control in a Murine Toxoplasmosis Model
title_full_unstemmed Preventive Anti-CD2 Treatment does not Impair Parasite Control in a Murine Toxoplasmosis Model
title_short Preventive Anti-CD2 Treatment does not Impair Parasite Control in a Murine Toxoplasmosis Model
title_sort preventive anti-cd2 treatment does not impair parasite control in a murine toxoplasmosis model
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4681358/
https://www.ncbi.nlm.nih.gov/pubmed/26716019
http://dx.doi.org/10.1556/1886.2015.00040
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