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The effect of interleukin-7 on the alloreactivity of human T cells depends on the timing of its administration in relation to the allostimulus

Bone Marrow Transplantation volume 35, pages 733–734 (2005)Cite this article

Interleukin-7 (IL-7), a potent thymopoietic cytokine, has the potential to restore impaired immune reconstitution, a major clinical problem limiting the success of allogeneic hematopoietic stem cell transplantation (HSCT).1 However, its effects on mature T-cell function may have an impact on graft rejection and graft-versus-host disease (GVHD) that would potentially outweigh the intended benefits. The impact of IL-7 in murine HSCT models is controversial, with IL-7 administration both worsening GVHD in some models,2 and selectively expanding nonalloreactive mature T cells, with no effect on GVHD in others.3, 4 IL-7 is being developed for clinical use in HSCT. However, its effect on the alloreactivity of human T cells remains unknown.

Although these results have the limitations of any in vitro studies, they show that human T cells downregulate IL-7R upon allostimulation, which modulates their response to exogenous IL-7 in vitro. This suggests that, in humans, the timing of IL-7 administration in relation to the allostimulus following allogeneic HSCT may determine the functional outcome in terms of alloreactivity, GVHD and response to other third-party antigens. Thus, such timing must be taken into consideration carefully in the forthcoming development and the design of HSCT trials with IL-7 in humans.

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Authors and Affiliations

  1. The Anthony Nolan Research Institute, London, UK

    R F Duarte & J A Madrigal

  2. Department of Haematological Medicine, King's College Hospital, London, UK

    R F Duarte & G J Mufti

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  1. R F Duarte
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  2. G J Mufti
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  3. J A Madrigal
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Duarte, R., Mufti, G. & Madrigal, J. The effect of interleukin-7 on the alloreactivity of human T cells depends on the timing of its administration in relation to the allostimulus. Bone Marrow Transplant 35, 733–734 (2005). https://doi.org/10.1038/sj.bmt.1704876

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