Immune reconstitution and implications for immunotherapy following haematopoietic stem cell transplantation - PubMed (original) (raw)

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Immune reconstitution and implications for immunotherapy following haematopoietic stem cell transplantation

Kirsten M Williams et al. Best Pract Res Clin Haematol. 2008 Sep.

Abstract

Recovery of a fully functional immune system is a slow and often incomplete process following allogeneic stem cell transplantation. While innate immunity reconstitutes quickly, adaptive B- and especially T-cell lymphopoeisis may be compromised for years following transplantation. In large part, these immune system deficits are due to the decrease, or even absence, of thymopoiesis following transplantation. Thereby, T-cell reconstitution initially relies upon expansion of mature donor T cells; a proliferation driven by high cytokine levels and the presence of allo-reactive antigens. This peripheral mechanism of T-cell generation may have important clinical consequences. By expanding tumouricidal T cells, it may provide a venue to enhance T-cellular immunotherapy following transplantation. Alternatively, decreased thymic function may impair long-term anti-tumour immunity and increase the likelihood of graft-versus-host disease.

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Figures

Figure 1

Figure 1

Representative time lines of immune reconstitution in adult patients without extensive graft-versus-host disease, infections or relapse. NK, natural killer; DC, dendritic cells.,,,,-,,,

Figure 2

Figure 2

Diagrammatic representation of the clinical consequences of the two types of T-cell reconstitution evident in the post-transplant period. Early after stem cell infusion, homeostatic proliferation drives the T-cell repertoire due to the high levels of cyokines and delayed thymic recovery. As a result, T cells in the donor product expand and mature into the memory pool, leading to an expanded memory pool with decreased diversity in both naïve and memory lymphocytes. Given the rapid proliferation of few T cells, this immediate post-transplant period presents an opportunity for immunotherapy, through the administration of tumour-targeted T cells or through vaccine administration. Later, in patients with the potential for thymic recovery [including younger patients without graft-versus-host disease (GvHD)], renewed thymopoiesis enriches the naïve T-cell pool. Due to the T-cell receptor re-arrangement in the thymus, these recent thymic emigrants enhance the diversity of the naïve, and subsequently the memory, T-cell repertoire (diagrammatically shown as multi-patterned cells). This has significant implications for long-term immunity. Not only are these patients less prone to life-threatening infections and GvHD, the enhanced T-cell diversity and renewed CD4+ cells likely confer improved tumour immunosurveillance, as shown by decreased rates of tumour relapse. HPE, homeostatic peripheral expansion; TREC, T-cell receptor re-arrangement excision circle; IL, interleukin; Treg, regulatory T cells.

References

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