Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain
the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in
Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles
and JavaScript.
The fact that many patients who have undergone high-dose therapy with autologous stem cell support are long-term survivors makes studies on possible late effects important. Hence, we appreciate Laurenti and co-workers′ comments on long-term immunological reconstitution after PBSCT. In this issue of Bone Marrow Transplant they present interesting data showing that subsets of lymphocytes are still altered several years after treatment. Like Laurenti, we observed that levels of CD4+ T cells and CD4/CD8 ratios were below normal levels in a group of lymphoma patients 4–10 years post ABMT.1 Both studies report normal numbers of CD8+ cells and a moderate increase in B cells. In our study, a higher percentage of stimulated CD4 + T cells produced IL-4 compared to controls, indicating a dominant Th2 response. This might help explain why numbers of B cells are increased. Unlike Laurenti and colleagues, we could not detect levels of NK cells above normal. These two reports are of particular importance because they are the first to investigate alterations in the immune system more than 5 years after high-dose therapy. It is interesting to observe that the situation after ABMT and PBSCT seems to be very similar.
By comparing three groups of patients at different time points after PBSCT, Laurenti was able to observe a trend towards recovery of CD4+ T cells and normalization of CD4/CD8 ratios. A similar observation was made in our previous study comparing patients transplanted 4–6 years and 7–10 years ago. Data are shown in Table 1. There was not, however, complete restoration, even in the group with the longest follow-up. When looking at subsets of CD4+ T cells, the ABMT patients had a significantly higher fraction of the CD45RO (memory) subset compared to controls, whereas the CD45RA (naive) subset was reduced (Table 1). No tendency towards normalization of this imbalance could be found when comparing patients transplanted 4–6 and 7–10 years ago. This supports the notion that maturation of T cells in the thymus is permanently impaired in adults and questions whether normal numbers of naive and memory T cells can ever be restored. Numbers in T cell subsets are altered many years after PBSCT and ABMT, but perhaps more important might be their function. We made an attempt to investigate this by looking at the production of cytokines after mitogen stimulation in CD4+ CD45RA+ and CD4+ CD45RO+ cells (Table 1). The percentage of cells producing γIFN or IL-4 was increased compared to controls and no tendency toward normalization could be observed. In addition, the patients have completed a vaccination program and these results will add information regarding immune function. We conclude, that even though the data indicate that recovery of CD4 + cells and CD8 + cells might take place over time, this does not necessarily mean that levels of naive (CD45RA) and memory (CD45RO) T cells normalize. Furthermore, there might be more permanent alterations in T cell function. A longer follow-up of patients after ABMT and PBSCT is important to find out whether the immune system is indeed completely restored.
