{'fraction_non_alphanumeric': 0.04360313315926893, 'fraction_numerical': 0.030287206266318537, 'mean_word_length': 4.921174652241112, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Immune recovery predicts survival after T-cell depleted allogeneic hematopoietic cell transplantation

T-cell recovery after allogeneic hematopoietic stem cell transplantation (allo-HCT) depends on both homeostatic peripheral expansion (HPE) of donor T cells contained in the graft [1], and T-cell neo-production from donor hematopoietic stem cells (thymusdependent pathway) [2,3]. Most circulating T cells during the first months after transplantation arise through HPE and are the progeny of T cells infused with the graft [1]. As a consequence of the lymphopenia caused by the conditioning regimen, IL-7 and IL-15 are not consumed and excess amounts of these cytokines affect HPE in specific cell subsets. While IL-7 and T-cell receptor (TCR) engagement are necessary for HPE of naive CD4þT cells, naive CD8þT cells can also proliferate in response to high amounts of IL-15 and IL-2 and TCR interactions. Memory CD4þT cells require only IL-7, HPE of memory CD8þT cells requires mainly IL-15. These discrepancies between CD4þand CD8þT cell HPE may explain partially the fact that HPE is more effective for CD8þ than for CD4þT cells. Beyond day 100, neo-generation of T cells by the thymus plays a progressively increasing role in reconstituting the T-cell pool [3,4]. However, previous studies have demonstrated that the thymusdependent pathway of T-cell generation plays a significant role only in patients younger than 60 years of age at transplantation and is affected by the occurrence of acute and extensive chronic graft-versus-host disease (GVHD) [5–8]. In the current issue of the journal, Goldberg et al. report the results of a retrospective study assessing kinetics of NK and T-cell recovery and their impact on relapse and survival in a large cohort of 375 recipients of myeloablative T-cell depleted allo-HCT from HLAmatched related (n1⁄4 202) or unrelated (n1⁄4 77) donors, or 1 antigen HLA-mismatched donors (n1⁄4 96) [9] (Figure 1). Grafts consisted of T-cell depleted bone marrow (BM, n1⁄4 190), T-cell depleted peripheral blood stem cells (PBSC, n1⁄4 153) or both (n1⁄4 32). T-cell depletion was carried out by positive selection of CD34þ cells, and 301 patients were further given in vivo T-cell depletion with horseor rabbit-ATG. None of the patients received postgrafting GVHD prophylaxis. As previously observed after T-cell replete allo-HCT [2,3,8,10], there was a rapid normalization of NK cells the first month after allo-HCT. T-cell recovery occurred in concordance with mechanisms of HPE described above and similar to what is observed in patients given T-cell replete grafts [2,3,8,10]. CD8þT cells recovered before total CD4þT cells – specifically, median total CD8þT cell count was already above the lower limit of normal at 6 months post-transplantation while 70% of the patients had still total CD4þT cell counts below normal at 1 year after transplantation. Interestingly, median naive CD4þT cell counts were 3 cells/mm (range, 0–177 cells/mm) at 6 months and 40 cells/mm (range, 0–748 cells/mm) at 12 months, indicating that neo-generation of T cells by the thymus was restored during the first year after transplantation. This prompt thymic recovery was probably favored by the fact that patients included in this study were relatively young (median age of 40 years, range 2–68 years), by the absence of post-transplant calcineurin inhibitors, and the low incidence of grades II–IV acute (18%) and chronic (9%) GVHD. Finally, functional T-cell responses (assessed by T-cell response to PHA) mirrored total CD4þT cell recovery. Several transplantation factors impacted T-cell recovery in the Goldberg et al. study. In concordance with prior observations [8,11], ATG administration was associated with delayed recovery of total CD4þT cells, naive CD4þT cells and T-cell function. Younger patient