Identification of non-naïve CD4+CD45RA+ T cell subsets in adult allogeneic haematopoietic cell transplant recipients

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.