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Lymphoid Reconstitution

Factors affecting reconstitution of the T cell compartment in allogeneic haematopoietic cell transplant recipients

Bone Marrow Transplantation volume 32, pages 1001–1014 (2003)Cite this article

Summary:

The factors affecting T cell reconstitution post haematopoietic cell transplantation (HCT) are not well characterised. We carried out a longitudinal analysis of T cell reconstitution in 32 HCT recipients during the first 12 months post transplant. We analysed reconstitution of naïve, memory and effector T cells, their diversity and monitored thymic output using TCR rearrangement excision circles (TRECs). Thymic-independent pathways were responsible for the rapid reconstitution of memory and effector T cells less than 6 months post HCT. Thymic-dependent pathways were activated between 6 and 12 months in the majority of patients with naïve T cell numbers increasing in parallel with TREC levels. Increasing patient age, chronic GVHD and T cell depletion (with or without pretransplant Campath-1H) predicted low TREC levels and slow naïve T cell recovery. Furthermore, increasing patient age also predicted high memory and effector T cell numbers. The effects of post HCT immunosuppression, total body irradiation, donor leucocyte infusions, T cell dose and post HCT infections on T cell recovery were also analysed. However, no effects of these single variables across a variety of different age, GVHD and T cell depletion groups were apparent. This study suggests that future analysis of the factors affecting T cell reconstitution and studies aimed at reactivating the thymus through therapeutic intervention should be analysed in age-, GVHD- and TCD-matched patient groups.

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Acknowledgements

We thank Dr Daniel Douek for providing TREC standard constructs and offering helpful advice in optimising the TREC assay, the clinical and nursing staff of the BMT team at the Royal Free Hospital for help in collecting patient samples and providing access to the BMT database and Dr Rose Zamoyska for critically reviewing this manuscript.

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  1. P R Fallen

    Present address: The Scripps Research Institute, Department of Immunology, La Jolla, CA, 92037, USA

  2. L McGreavey

    Present address: Ninewells Hospital and Medical School, Biomedical Research Institute, Dundee, DD1 9SY, UK

Authors and Affiliations

  1. Anthony Nolan Research Institute, Fleet Road, London, UK

    P R Fallen, L McGreavey, J A Madrigal & P J Travers

  2. Department of Haematology, Royal Free and University College Medical School, Royal Free Campus, Rowland Hill Street, Hampstead, London, UK

    J A Madrigal, M Potter, M Ethell, H G Prentice & P J Travers

  3. Unidade de Transplante de Medula Óssea, Instituto Português de Oncologia, Centro de Lisboa, Portugal

    A Guimarães

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Fallen, P., McGreavey, L., Madrigal, J. et al. Factors affecting reconstitution of the T cell compartment in allogeneic haematopoietic cell transplant recipients. Bone Marrow Transplant 32, 1001–1014 (2003). https://doi.org/10.1038/sj.bmt.1704235

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