B cell depletion with anti-CD20 mAb exacerbates anti-donor CD4+ T cell responses in highly sensitized transplant recipients

Abstract Pretransplant desensitization with rituximab has been applied to preformed donor-specific anti-human leukocyte antigen antibody (DSA)-positive recipients for elimination of preformed DSA. We investigated the impact of pretransplant desensitization with rituximab on anti-donor T cell respons...

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Autores principales:	Asuka Tanaka, Kentaro Ide, Yuka Tanaka, Masahiro Ohira, Hiroyuki Tahara, Hideki Ohdan
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c89d3458969540d983553771f2aba80f
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spelling	oai:doaj.org-article:c89d3458969540d983553771f2aba80f2021-12-02T18:33:47ZB cell depletion with anti-CD20 mAb exacerbates anti-donor CD4+ T cell responses in highly sensitized transplant recipients10.1038/s41598-021-97748-92045-2322https://doaj.org/article/c89d3458969540d983553771f2aba80f2021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97748-9https://doaj.org/toc/2045-2322Abstract Pretransplant desensitization with rituximab has been applied to preformed donor-specific anti-human leukocyte antigen antibody (DSA)-positive recipients for elimination of preformed DSA. We investigated the impact of pretransplant desensitization with rituximab on anti-donor T cell responses in DSA-positive transplant recipients. To monitor the patients’ immune status, mixed lymphocyte reaction (MLR) assays were performed before and after desensitization with rituximab. Two weeks after rituximab administration, the stimulation index (SI) of anti-donor CD4+ T cells was significantly higher in the DSA-positive recipients than in the DSA-negative recipients. To investigate the mechanisms of anti-donor hyper responses of CD4+ T cells after B cell depletion, highly sensitized mice models were injected with anti-CD20 mAb to eliminate B cells. Consistent with clinical observations, the SI values of anti-donor CD4+ T cells were significantly increased after anti-CD20 mAb injection in the sensitized mice models. Adding B cells isolated from untreated sensitized mice to MLR significantly inhibited the enhancement of anti-donor CD4+ T cell response. The depletion of the CD5+ B cell subset, which exclusively included IL-10-positive cells, from the additive B cells abrogated such inhibitory effects. These findings demonstrate that IL-10+ CD5+ B cells suppress the excessive response of anti-donor CD4+ T cells responses in sensitized recipients.Asuka TanakaKentaro IdeYuka TanakaMasahiro OhiraHiroyuki TaharaHideki OhdanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Asuka Tanaka Kentaro Ide Yuka Tanaka Masahiro Ohira Hiroyuki Tahara Hideki Ohdan B cell depletion with anti-CD20 mAb exacerbates anti-donor CD4+ T cell responses in highly sensitized transplant recipients
description	Abstract Pretransplant desensitization with rituximab has been applied to preformed donor-specific anti-human leukocyte antigen antibody (DSA)-positive recipients for elimination of preformed DSA. We investigated the impact of pretransplant desensitization with rituximab on anti-donor T cell responses in DSA-positive transplant recipients. To monitor the patients’ immune status, mixed lymphocyte reaction (MLR) assays were performed before and after desensitization with rituximab. Two weeks after rituximab administration, the stimulation index (SI) of anti-donor CD4+ T cells was significantly higher in the DSA-positive recipients than in the DSA-negative recipients. To investigate the mechanisms of anti-donor hyper responses of CD4+ T cells after B cell depletion, highly sensitized mice models were injected with anti-CD20 mAb to eliminate B cells. Consistent with clinical observations, the SI values of anti-donor CD4+ T cells were significantly increased after anti-CD20 mAb injection in the sensitized mice models. Adding B cells isolated from untreated sensitized mice to MLR significantly inhibited the enhancement of anti-donor CD4+ T cell response. The depletion of the CD5+ B cell subset, which exclusively included IL-10-positive cells, from the additive B cells abrogated such inhibitory effects. These findings demonstrate that IL-10+ CD5+ B cells suppress the excessive response of anti-donor CD4+ T cells responses in sensitized recipients.
format	article
author	Asuka Tanaka Kentaro Ide Yuka Tanaka Masahiro Ohira Hiroyuki Tahara Hideki Ohdan
author_facet	Asuka Tanaka Kentaro Ide Yuka Tanaka Masahiro Ohira Hiroyuki Tahara Hideki Ohdan
author_sort	Asuka Tanaka
title	B cell depletion with anti-CD20 mAb exacerbates anti-donor CD4+ T cell responses in highly sensitized transplant recipients
title_short	B cell depletion with anti-CD20 mAb exacerbates anti-donor CD4+ T cell responses in highly sensitized transplant recipients
title_full	B cell depletion with anti-CD20 mAb exacerbates anti-donor CD4+ T cell responses in highly sensitized transplant recipients
title_fullStr	B cell depletion with anti-CD20 mAb exacerbates anti-donor CD4+ T cell responses in highly sensitized transplant recipients
title_full_unstemmed	B cell depletion with anti-CD20 mAb exacerbates anti-donor CD4+ T cell responses in highly sensitized transplant recipients
title_sort	b cell depletion with anti-cd20 mab exacerbates anti-donor cd4+ t cell responses in highly sensitized transplant recipients
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/c89d3458969540d983553771f2aba80f
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B cell depletion with anti-CD20 mAb exacerbates anti-donor CD4+ T cell responses in highly sensitized transplant recipients

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