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The roles of IL-2 and IL-10 enhance anti-CD45RBmAb immune inhibition in allograft skin

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Abstract

As a new type of immune tolerance inducer, anti-CD45RB monoclonal antibodies (anti-CD45RBmAb) can prolong the graft survival time of animal organs or cell transplantation as well as induce stable immune tolerance. Both interleukin (IL)-2 and IL-10 have important roles in the induction and maintenance of immunological tolerance. However, whether these cytokines combined with anti-CD45RBmAb can promote immune tolerance is poorly understood. Therefore, we investigated the effect of IL-2 and IL-10 in vitro and in vivo on the tolerance induction by anti-CD45RBmAb. The changes of Treg and Th17 cells and Th1/Th2 cytokines in anti-CD45RBmAb induced prolongation of skin allograft survival in mice. The finding of a role for IL-2 is novel, of interest, IL-2 promoted anti-CD45RBmAb-induced CD4+ T cell differentiation into Treg and Th2 cells and suppressed Th17 and Th1 cells. IL-2 enhanced the induction of immune tolerance by anti-CD45RBmAb and significantly prolonged skin graft survival time in vivo. In contrast, this effect should be demonstrated experimentally by neutralizing IL-2 and inhibition of the effect of anti-CD45RBmAb, and neutralizing IL-10 showed no effect for anti-CD45RBmAb-induced tolerance. These data reveal that IL-2 significantly enhances anti-CD45RBmAb-induced immune tolerance via up-regulated T regulatory (Treg) cells and the balance of Th1/Th2 shifts. Conversely, IL-10 showed no effect on anti-CD45RBmAb-induced tolerance.

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Acknowledgments

This work was supported by the national 973 special plan of China (No. 2007CB516811), the National Natural Science Foundation of China (No. 30772042), The Natural Science Foundation of Guangdong (No. 6027540) and The Science and Technology Project of Shenzhen (No. 201001005).

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No competing financial interests exist.

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Authors and Affiliations

  1. The Key Laboratory of Stem Cell and Cellular Therapy, the Second Clinical Medical College (Shenzhen People’s Hospital), Ji’nan University, Nu.1017, North Road of Eastern Gate, Shenzhen, 518020, China

    Wei-Jian Guo, Hui Qi, Chun-Yan Deng & Fu-Rong Li

  2. Shenzhen Institute of Gerontology, Shenzhen, 518020, China

    Han-Xin Zhou & Fu-Rong Li

  3. Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Shao-Ping Deng

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  1. Wei-Jian Guo
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  2. Hui Qi
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Correspondence to Shao-Ping Deng or Fu-Rong Li.

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Guo, WJ., Qi, H., Deng, CY. et al. The roles of IL-2 and IL-10 enhance anti-CD45RBmAb immune inhibition in allograft skin. Immunol Res 61, 250–259 (2015). https://doi.org/10.1007/s12026-014-8618-9

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  • DOI: https://doi.org/10.1007/s12026-014-8618-9

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