Arsenic trioxide is a novel agent for combination therapy to prolong heart allograft survival in allo-primed T cells transferred mice
| Autor: | Yingying Lin, Guoliang Yan, Jibing Chen, Henrik Ekberg, Yanfeng Xi, Helong Dai, Zhongquan Qi, Jingjun Su |
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| Rok vydání: | 2011 |
| Předmět: |
Adoptive cell transfer
Combination therapy medicine.drug_class T-Lymphocytes Immunology Antineoplastic Agents chemical and pharmacologic phenomena Monoclonal antibody Arsenicals Antibodies Monoclonal Murine-Derived Interferon-gamma Mice chemistry.chemical_compound Arsenic Trioxide Animals Transplantation Homologous Immunology and Allergy Medicine CD154 Arsenic trioxide Cell Proliferation Mice Inbred BALB C Transplantation biology business.industry Graft Survival Heart Oxides hemic and immune systems Adoptive Transfer Antibodies Neutralizing chemistry Lymphocyte Transfusion Monoclonal Cancer research biology.protein Heart Transplantation Interleukin-2 Female Antibody business Spleen |
| Zdroj: | Transplant Immunology. 25:194-201 |
| ISSN: | 0966-3274 |
| Popis: | Alloreactive memory T cells are major barriers to transplantation acceptance due to their capacity to accelerate rejection. Here, we investigated the effects of combined treatment with arsenic trioxide (As(2)O(3)) and blocking monoclonal antibodies (mAb) against CD154 and LFA-1 (anti-CD154/LFA-1) on graft survival as well as changes in pathology and immunological responses in mice with adoptively transferred allo-primed T cells. The mean survival time (MST) for the cardiac allografts in recipient mice receiving the combination of As(2)O(3) and anti-CD154/LFA-1 was significantly longer (>113.7days) compared to those receiving anti-CD154/LFA-1 (23.2days), As(2)O(3) (12.5days) alone or no treatment (5.5days). This combined strategy distinctly inhibited lymphocyte infiltration in grafts, proliferation of splenic T cells and the generation of memory T cells in spleens. Moreover, the combined treatment caused the significant down-regulation of IL-2 and IFN-γ accompanied by increased expression of TGF-β and regulatory T cells (Tregs) in spleens, which led to long-term cardiac allograft survival in recipient mice. These results highlight the potential application of As(2)O(3) and its contribution in combination therapy with antibody blockade to delay rejection by memory T cells. |
| Databáze: | OpenAIRE |
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