Shaping of iNKT cell repertoire after unrelated cord blood transplantation

Béziat, Vivien; Nguyen, Stéphanie; Exley, Mark A.; Achour, Abla; Simon, Tabassome; Chevallier, Patrice; Sîrvent, Anne; Vigouroux, Stéphane; Debré, Patrice; Rio, Bernard; Vieillard, Vincent

doi:10.1016/j.clim.2010.01.010

Cited by 22 publications

(22 citation statements)

References 55 publications

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“…The possible correlation between iNKT cell reconstitution and remission was not addressed, although one study suggested that a low number of iNKT cells could be related to the development of GVHD (36). Both studies were performed in adult patients receiving either T cell-replete HLA-matched allogeneic HSC or umbilical cord blood (36,37), and thus required posttransplantation treatment with immune-suppressive drugs to prevent GVHD. This faster iNKT cell reconstitution dynamics could depend, at least in patients given HLA-matched HSC, on the adoptive transfer of donor-derived mature lymphocytes present in the graft and/or the different transplantation protocols used in these studies, as compared with our approach of T cell depletion of the graft.…”

Section: Discussionmentioning

confidence: 99%

“…3B, which were 0.13 and 0. 37 To assess the kinetics of effector differentiation by reconstituting iNKT cells, we investigated their capacity to produce IFN-g and IL-4 ex vivo on a brief stimulation. Previous studies showed that the frequency of human iNKT cells producing IFN-g increases from 10-20% at birth to 50-60% in adults, suggesting that these cells acquire full effector functions only late after birth (20,22).…”

Section: Post-hhsct With Different Dynamicsmentioning

confidence: 99%

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Invariant NKT Cell Reconstitution in Pediatric Leukemia Patients Given HLA-Haploidentical Stem Cell Transplantation Defines Distinct CD4+ and CD4− Subset Dynamics and Correlates with Remission State

Lalla

Rinaldi

Montagna

et al. 2011

The Journal of Immunology

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Immune reconstitution plays a crucial role on the outcome of patients given T cell-depleted HLA-haploidentical hematopoietic stem cell transplantation (hHSCT) for hematological malignancies. CD1d-restricted invariant NKT (iNKT) cells are innate-like, lipid-reactive T lymphocytes controlling infections, cancer, and autoimmunity. Adult mature iNKT cells are divided in two functionally distinct CD4+ and CD4− subsets that express the NK receptor CD161 and derive from thymic CD4+CD161− precursors. We investigated iNKT cell reconstitution dynamics in 33 pediatric patients given hHSCT for hematological malignancies, with a follow-up reaching 6 y posttransplantation, and correlated their emergence with disease relapse. iNKT cells fully reconstitute and rapidly convert into IFN-γ–expressing effectors in the 25 patients maintaining remission. CD4+ cells emerge earlier than the CD4− ones, both displaying CD161− immature phenotypes. CD4− cells expand more slowly than CD4+ cells, though they mature with significantly faster kinetics, reaching full maturation by 18 mo post-hHSCT. Between 4 and 6 y post-hHSCT, mature CD4− iNKT cells undergo a substantial expansion burst, resulting in a CD4+<CD4− NKT cell ratio similar to that found in healthy adults. In contrast with patients maintaining remission, iNKT cells failed to reconstitute in all eight patients experiencing disease relapse. These findings define the peripheral dynamics of human iNKT cells and suggest a contribution of these cells to maintain remission, possibly via early IFN-γ provision. Adoptive transfer of donor-derived iNKT cells into HLA-haploidentical patients failing to reconstitute these cells might represent a novel therapeutic option to prevent leukemia recurrence.

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Section: Discussionmentioning

confidence: 99%

Section: Post-hhsct With Different Dynamicsmentioning

confidence: 99%

Invariant NKT Cell Reconstitution in Pediatric Leukemia Patients Given HLA-Haploidentical Stem Cell Transplantation Defines Distinct CD4+ and CD4− Subset Dynamics and Correlates with Remission State

Lalla

Rinaldi

Montagna

et al. 2011

The Journal of Immunology

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“…Potentially increased GVL effect without marked increase in GVHD [9][10][11][12] iNKT cells 1 month (CBT or PBSCT without ATG [13,14]) to…”

Section: Key Pointsmentioning

confidence: 99%

“…All these complications are due at least in part to immune deficiency or dysregulation. Here we review how various components of the immune system recover (summarized in Table 1 [1][2][3][4][5][6][7]8 & , [9][10][11][12][13][14][15][16][17][18][19][20][21][22], [55][56][57][58][59][60][61][62][63][64][65][66][67][68][69][70][71][72]). Additional in depth reviews on immune reconstitution can be found elsewhere [21,[72][73][74][75].…”

Section: Introductionmentioning

confidence: 99%

Immune reconstitution after hematopoietic cell transplantation

Bosch

Khan

Storek

2012

Current Opinion in Hematology

186

172

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“…In another study, iNKT cells were reconstituted within a month after umbilical cord blood transplantation (UCBT). 87 Taken together, these studies indicate that the graft composition of iNKT cells in BM, PBSC and CB are different, which may impact the kinetics of iNKT-cell reconstitution as well as their repertoire in the transplant recipients.…”

Section: Role Of Human Inkts In Clinical Gvhdmentioning

confidence: 84%