Effects of CD25 monoclonal antibody on proliferative and effector functions of alloactivated human T cells in vitro

Authors

  • Ajda T. Rowshani,

    Corresponding author
    1. Division of Clinical Immunology and Rheumatology, Academic Medical Center, Amsterdam, The Netherlands
    • Division of Clinical Immunology and Rheumatology, Department of Internal Medicine, Academic Medical Center, University of Amsterdam, PO Box 22700, 1100 DE Amsterdam, The Netherlands Fax: +31-20-6914904

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  • Alena Uss,

    1. Division of Clinical Immunology and Rheumatology, Academic Medical Center, Amsterdam, The Netherlands
    2. Laboratory for Experimental Immunology, Academic Medical Center, Amsterdam, The Netherlands
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  • Si-La Yong,

    1. Division of Clinical Immunology and Rheumatology, Academic Medical Center, Amsterdam, The Netherlands
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  • René A.W. van Lier,

    1. Laboratory for Experimental Immunology, Academic Medical Center, Amsterdam, The Netherlands
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  • Ineke J. M. ten Berge

    1. Division of Clinical Immunology and Rheumatology, Academic Medical Center, Amsterdam, The Netherlands
    2. Renal Transplant Unit, Department of Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands
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Abstract

Prophylactic treatment with CD25 mAb has led to a significant decrease of acute rejection rates after renal transplantation. However, despite its inhibitory effect on T cell proliferation and effector functions, rejections still occur. To obtain more insight in persistent alloreactivity, we evaluated the effects of the chimeric IgG1κ CD25 mAb Basiliximab® on proliferation and differentiation of alloactivated T cells from healthy individuals in vitro. Moreover, the capacity of other members of the common cytokine-receptor γ-chain family to overcome the inhibitory effects of CD25 mAb was studied. The CD25 mAb appeared to limit expansion of alloreactive lymphocytes rather than blocking entry into cell cycle, and it did so irrespective of the previous antigen experience of the cells. Both CD4+ and CD8+ alloresponsive lymphocytes showed diminished intracellular expression of IFN-γ, TNF-α, perforin and granzyme B. Remarkably, cytotoxicity was completely abolished. IL-7, IL-15 and IL-21 could bypass the inhibitory effects of the CD25 mAb on both proliferation and cytotoxicity. In conclusion, persistent alloreactivity in the presence of therapeutic concentrations of CD25 mAb may be caused by alloreactive T cells that still produce cytokines that can damage the allograft. In addition, other members of the common cytokine-receptor γ-chain family can rescue the proliferative and cytotoxic activity of these alloreactive T cells.

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