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Cyclophosphamide-modified murine peritoneal macrophages induce CD4+ T contrasuppressor cells that protect contact sensitivity T effector cells from suppression

Majewska-Szczepanik, Monika, Kowalczyk, Paulina, Biała, Dominika, Marcińska, Katarzyna, Strzępa, Anna, Woźniak, Dorota, Sura, Piotr, Pearson, James, Wen, Li and Szczepanik, Marian 2018. Cyclophosphamide-modified murine peritoneal macrophages induce CD4+ T contrasuppressor cells that protect contact sensitivity T effector cells from suppression. Pharmacological Reports 70 (4) , pp. 796-803. 10.1016/j.pharep.2018.02.015

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Abstract

Background Cyclophosphamide (CY) is one of the most widely used alkylating agents in the treatment of various cancers and some autoimmune diseases. Numerous reports suggest that CY exerts immunoregulatory effects. Animal studies have shown CY affects contact sensitivity (CS) response by depleting CD4+CD25+ T regulatory cells and CD8+ T suppressor (Ts) cells. In a mouse model of CS, we previously showed that in vivo treatment with CY shapes the immunogenic/immunoregulatory balance of peritoneal macrophages. The aim of the current study is to verify if macrophages (Mf) from CY-treated mice are indeed able to induce immunoregulatory cells that could protect from suppression. Methods Adoptive cell transfer of CS was used to examine immunomodulating properties of peritoneal Mf from CY-treated mice. Isolation of peritoneal Mf from animals that were (Mf-CY) or were not (Mf) treated with CY were cultured to identify cytokine repertoire. Further, we assessed spleen cell (SPLC) cytokine production following immunization with trinitrophenyl-conjugated Mf from donors treated (TNP-Mf-CY) or non-treated (TNP-Mf) with CY. Results In vitro experiments identified that Mf-CY produce more IL-6, TNF-α and TGF-β than naïve Mf. Further, immunization with peritoneal TNP-Mf-CY induces CD4+ T contrasuppressor cells (Tcs) cells that protect CS-effector cells from suppression. Higher IL-17A secretion was observed from TNP-Mf-CY-treated mouse SPLC compared to SPLC from TNP-Mf injected mice suggesting that this cytokine might be important in mediating contrasuppression in this model. Conclusions Our results show that in vivo treatment with CY influences mouse peritoneal Mf to induce CD4+ Tcs cells that protect CS-effector cells from suppressive signals of Ts cells.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Institute of Pharmcology Polish Academy of Sciences
ISSN: 1734-1140
Date of Acceptance: 19 February 2018
Last Modified: 13 May 2020 13:45
URI: http://orca-mwe.cf.ac.uk/id/eprint/131617

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