Summary:
The study of thymic-dependent pathways of T cell reconstitution in T cell replete haematopoietic cell transplant (HCT) recipients in previous studies was complicated by the transfer of naïve CD4+CD45RA+ T cells with the stem cell graft. However, direct quantification of thymic output has been enabled by measurement of T cell receptor excision circles (TREC). We analysed T cell reconstitution using T cell phenotyping and TREC quantification in 12 T cell-replete HCT recipients 6–53 years of age during the first 12 months post transplant. We have identified a novel subpopulation of CD4+CD45RA+ T cells in the peripheral blood of these HCT recipients with expansions of this subset being more pronounced in older recipients. The recovery of classical naïve CD4+CD45RA+ T cells was dependent on thymic output whereas this novel CD4+CD45RA+ subpopulation arose independently of thymic output and displayed effector function and phenotype. These results suggest that CD4+CD45RA+ effector populations exist, similar to the CD8+CD45RA+ effector subset, and that the CD45RA antigen should not be used alone to define naïve CD4+ T cells when monitoring T cell reconstitution in T cell replete HCT recipients. Furthermore, these results raise important questions regarding the role of the thymus in regulating T cell homeostasis in older HCT recipients and normal individuals.
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Acknowledgements
We would like to acknowledge Daniel Douek for help and advice in optimising the TREC assay; Sarah Grace and the nursing staff of Crowley Ward for taking blood samples, without whose cooperation this project would not have been possible; and Rose Zamoyska and Brigitta Stockinger for critically reviewing this manuscript.
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This work was supported by the Anthony Nolan Trust.
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Fallen, P., Duarte, R., McGreavey, L. et al. Identification of non-naïve CD4+CD45RA+ T cell subsets in adult allogeneic haematopoietic cell transplant recipients. Bone Marrow Transplant 32, 609–616 (2003). https://doi.org/10.1038/sj.bmt.1704185
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DOI: https://doi.org/10.1038/sj.bmt.1704185
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