Fully functional NK cells after unrelated cord blood transplantation

Béziat, Vivien; Nguyen, Stéphanie; Lapusan, Simona; Hervier, B.; Dhédin, Nathalie; Bories, Dominique; Uzunov, Madalina; Boudifa, Ali; Trébeden-Nègre, Hélène; Norol, Françoise; Marjanovic, Zora; Marie, Jean Pierre; Vernant, Jean‐Paul; Debré, Patrice; Rio, Bernard; Vieillard, Vincent

doi:10.1038/leu.2008.343

Cited by 52 publications

(62 citation statements)

References 51 publications

(72 reference statements)

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“…32 Similarly, our study confirmed the rapid recovery of NK cells after CBT. 29,30,36 It is of importance as NK cells are known to have potential effect on clinical outcomes in term of complications, GVHD or relapse. 36 This cell type is also one of the targets of HHV6, in which it can undergo a complete multiplication cycle 33 and thus may represent one of the source of the progeny viruses.…”

Section: Discussionmentioning

confidence: 99%

Human herpes virus 6 infection is a hallmark of cord blood transplant in adults and may participate to delayed engraftment: a comparison with matched unrelated donors as stem cell source

Chevallier

Hebia-Fellah²,

Planche

et al. 2009

Bone Marrow Transplant

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Occurrence of CMV, EBV and human herpes virus 6 (HHV6) infections and immune reconstitution were compared in 15 adult patients receiving a cord blood transplantation (CBT) and 40 patients who received an allogeneic transplantation from a matched unrelated donor (MUD). Herpes virus DNA quantifications in the blood (459 samples) were performed before and then monthly up to 9 months after transplant and the main lymphocytes populations were counted at 3, 6 and 9 months. Incidence of HHV6 infection was significantly higher in the CBT group (80 vs 42.5%; Po0.0001), with higher viral load (Po0.0001). In multivariate analysis, the use of a CBT and a myeloablative conditioning regimen were found to increase the risk of HHV6 infection (odds ratio (OR) ¼ 5.4, P ¼ 0.02 and OR ¼ 3.5, P ¼ 0.04, respectively). Incidences of CMV were similar between the two groups whereas MUD increased the risk of EBV infection, in univariate analysis only. HHV6 reactivation translated toward delayed neutrophils and plts engraftment in the two groups. MUD and CBT do not share the same immune reconstitution patterns, notably for B and CD8 lymphocytes and NK cells. There is a strong and specific relationship between HHV6 infection and the use of cord blood cells.

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Section: Discussionmentioning

confidence: 99%

Human herpes virus 6 infection is a hallmark of cord blood transplant in adults and may participate to delayed engraftment: a comparison with matched unrelated donors as stem cell source

Chevallier

Hebia-Fellah²,

Planche

et al. 2009

Bone Marrow Transplant

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“…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.…”

Section: Introductionmentioning

confidence: 99%

Reconstitution of maturating and regulatory lymphocyte subsets after cord blood and BMT in children

Charrier

Cordeiro

Brito

et al. 2012

Bone Marrow Transplant

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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.

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“…Direct cytotoxicity was assessed after IL-2 stimulation (proleukin-2, 1000 IU/ml) for 72 h, with a standard 4-h 51 Cr-release assay against the human leukocyte antigen (HLA) class I-deficient human K562 cell line. 21 Anti-CD20 LFB-R603 antibody LFB-R603 is a chimeric mAb directed against CD20 with a glycosylation profile that allows increased binding to CD16. This mAb has been granted an orphan-drug status in Europe and in the USA for CLL treatment (http://www.lfb.fr/en/home.html).…”

Section: Patients and Control Donorsmentioning

confidence: 99%

“…Cells were fixed and permeabilized with a cytofix/ cytoperm kit (BD Biosciences), and stained with IFN-g mAb (B27; BD Biosciences), as described. 21 Direct cytolytic activity of NK cells NK cell-enriched PBMC (8 CLL patients and 5 controls) were tested for direct cytotoxicity. NK cell-enriched PBMC fractions were obtained after negative depletion (anti-CD19-coated beads) followed by positive selection (anti-CD56-coated beads) (Miltenyi Biotec, Bergish Gladbach, Germany).…”

Section: Patients and Control Donorsmentioning

confidence: 99%

Analysis of CD16+CD56dim NK cells from CLL patients: evidence supporting a therapeutic strategy with optimized anti-CD20 monoclonal antibodies

et al. 2010

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Although anti-CD20 monoclonal antibodies (mAbs) show promise for the treatment of chronic lymphocytic leukemia (CLL), the success of the anti-CD20 mAb rituximab in CLL treatment has been limited. Novel anti-CD20 mAbs with more potent cytotoxic activity have recently been engineered, but so far most have only been tested in vitro with natural killer (NK) cells from healthy donors. Because it is still unclear whether these optimized cytotoxic mAbs will improve NK-cell killing of tumor cells in CLL patients, we characterized the relevant phenotypic and functional features of NK cells from CLL patients in detail. Expression of inhibitory and activating NK-cell receptors and of Fc gamma receptor IIIA (FccRIIIA) is well preserved in CD16 þ CD56 dim cytotoxic NK cells from these patients, independently of disease progression. These cells are fully functional following cytokine stimulation. In addition, the FccRIIIA-optimized LFB-R603 anti-CD20 mAb mediates 100 times greater antibody-dependent cell-mediated cytotoxicity by NK cells from CLL patients and healthy donors than rituximab. Enhanced degranulation against autologous B-CLL cells is observed at lower concentrations of LFB-R603 than rituximab, regardless of CLL prognostic factors. These findings strongly justify further clinical development of anti-CD20 mAbs optimized for FccR engagement in CLL patients.

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Fully functional NK cells after unrelated cord blood transplantation

Cited by 52 publications

References 51 publications

Human herpes virus 6 infection is a hallmark of cord blood transplant in adults and may participate to delayed engraftment: a comparison with matched unrelated donors as stem cell source

Human herpes virus 6 infection is a hallmark of cord blood transplant in adults and may participate to delayed engraftment: a comparison with matched unrelated donors as stem cell source

Reconstitution of maturating and regulatory lymphocyte subsets after cord blood and BMT in children

Analysis of CD16+CD56dim NK cells from CLL patients: evidence supporting a therapeutic strategy with optimized anti-CD20 monoclonal antibodies

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