Some clinical characteristics of cord blood transplantation (CBT) might be explained by specificities in the reconstitution of immune subsets differing by their maturation stage or their implication in GVHD, tolerance or immune responses against tumor or infectious agents. Here, we compare the immune reconstitution of several of these subsets after CBT and BMT. B-cell count recovery was faster after CBT. There was no difference in the recovery of CD4 þ and CD8 þ cell counts. There was no difference either in the frequency of several subsets: CD45RO þ memory, and CD45RA þ naïve cells within the CD4 þ T-cell compartment, CD27 þ among B cells, CD56 bright , NKG2A þ , and KIR þ cells among natural killer (NK) cells, CD25 þ FOXP3 þ regulatory T cells and invariant NKT cells. The proportion of the thymic naïve CD31 þ CD45RA þ CD4 þ T cells was lower after CBT at 6 months post-transplant, and was still below normal at 1 year in both groups. NK-cell expansion was more sustained after CBT, with fewer double-negative NKG2A À KIR À hyporesponsive cells and more double-positive NKG2A þ KIR þ hyper-responsive NK cells. These results, therefore, indicate that further research to improve CBT outcome should try to improve thymopoieisis and take advantage of the sustained NK-cell reconstitution. INTRODUCTIONAlmost all lethal complications of hematopoietic SCT, including leukemia relapse, and opportunistic infections, result from the post-transplant immune deficiency that lasts for months after transplantation. Therefore, the therapeutic challenge in improving the outcome for transplanted children outcome relies on the enhancement of immune reconstitution and the GVL effect, without increasing the harmful GVHD.Although lower rates of engraftment and GVHD and higher rates of life-threatening infections have been reported in patients who received cord blood transplantation (CBT), similar EFS and leukemia relapse rates have been observed after CBT and BMT. [1][2][3][4][5] These observations indicate that cord blood-derived immune cells have unique immune properties that allow for allogeneic tolerance while preserving the GVL effect.Previous studies have compared the reconstitution of the major immune cell populations after CBT and BMT: CD4 þ and CD8 þ T cells, natural killer (NK) and B cells. They showed that T-cell recovery is delayed, in particular CD8 þ T-lymphopoiesis after CBT, 2,6-9 although T-cell diversity has been shown to be similar in cord blood (CB) and BM recipients beyond 1 year after transplant. 7,10 Conversely, innate immunity recovery has been shown to be similar between CB and BM recipients, with normal cell counts of functional NK cells in the blood as soon as 1-month post-CBT. 2,11,12 Finally, B-cell number recovery appears to be faster after CBT. 6,9,13 Besides these differences in the reconstitution of the major lymphocyte populations, additional changes in the reconstitution of other immune cell subsets might occur and explain some of the clinical differences observed in patients who receive BMT or CBT.