Similar Potential to Become Activated and Proliferate but Differential Kinetics and Profiles of Cytokine Production of Umbilical Cord Blood T Cells and Adult Blood Naive and Memory T Cells

Kloosterboer, Freke M.; Luxemburg-Heijs, Simone A.P. van; Willemze, R.; Falkenburg, J.H. Frederik

doi:10.1016/j.humimm.2006.02.040

Cited by 17 publications

(15 citation statements)

References 27 publications

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“…In contrast, expression levels of IL2 , IFNG , and IL17A were not increased following either CD26 costimulation or CD28 costimulation (Fig. 4A), due to the immaturity of HuCB T cells, as was previously reported (21, 48). We next conducted costimulatory experiments evaluating dose effect and time kinetics using the CD26 costimulatory ligand Cav-Ig as well as anti-CD26 or anti-CD28 mAbs, and assayed for secreted IL-26.…”

Section: Resultssupporting

confidence: 71%

Regulation of Pulmonary Graft-versus-Host Disease by IL-26+CD26+CD4 T Lymphocytes

Ohnuma

Hatano

Aune

et al. 2015

The Journal of Immunology

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Obliterative bronchiolitis is a potentially life-threatening noninfectious pulmonary complication after allogeneic hematopoietic stem cell transplantation and the only pathognomonic manifestation of pulmonary chronic graft-versus-host disease (cGVHD). In the current study, we identified a novel effect of IL-26 on transplant-related obliterative bronchiolitis. Sublethally irradiated NOD/Shi-scidIL2rγnull mice transplanted with human umbilical cord blood (HuCB mice) gradually developed clinical signs of graft-versus-host disease (GVHD) such as loss of weight, ruffled fur, and alopecia. Histologically, lung of HuCB mice exhibited obliterative bronchiolitis with increased collagen deposition and predominant infiltration with human IL-26+CD26+CD4 T cells. Concomitantly, skin manifested fat loss and sclerosis of the reticular dermis in the presence of apoptosis of the basilar keratinocytes, whereas the liver exhibited portal fibrosis and cholestasis. Moreover, although IL-26 is absent from rodents, we showed that IL-26 increased collagen synthesis in fibroblasts and promoted lung fibrosis in a murine GVHD model using IL-26 transgenic mice. In vitro analysis demonstrated a significant increase in IL-26 production by HuCB CD4 T cells following CD26 costimulation, whereas Ig Fc domain fused with the N-terminal of caveolin-1 (Cav-Ig), the ligand for CD26, effectively inhibited production of IL-26. Administration of Cav-Ig before or after onset of GVHD impeded the development of clinical and histologic features of GVHD without interrupting engraftment of donor-derived human cells, with preservation of the graft-versus-leukemia effect. These results therefore provide proof of principle that cGVHD of the lungs is caused in part by IL-26+CD26+CD4 T cells, and that treatment with Cav-Ig could be beneficial for cGVHD prevention and therapy.

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Section: Resultssupporting

confidence: 71%

Regulation of Pulmonary Graft-versus-Host Disease by IL-26+CD26+CD4 T Lymphocytes

Ohnuma

Hatano

Aune

et al. 2015

The Journal of Immunology

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“…As currently described, CB contains only little Functional NK cells after UCBT V Beziat et al or no cytotoxic T cells directed against viral and bacterial peptides, which may cross-react with HLA alloantigens, and thus may be responsible for the lower-than-expected frequency of severe GvH disease, even in the setting of one or two HLA mismatched. 46,47 Similarly, in this study, less than 32% of patients presented an acute grade II or III GvH disease, and no patient presented an acute grade IV graft-versus-host disease, which could be due to the lack of post-thymic T cells and the naivety of the T-cell function after UCBT observed earlier after haploidentical HSCT. 48,49 However, we have shown earlier that following haploidentical HSCT, relapse occurred in the early post-transplantation period in 7-10 patients (70%), despite the KIR-ligand incompatibility between donor and recipient.…”

Section: Discussionsupporting

confidence: 51%

Fully functional NK cells after unrelated cord blood transplantation

et al. 2009

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Promising results of umbilical cord blood transplantation (UCBT) from unrelated donors have been reported in patients with hematologic disorders. These transplants, having potential to trigger beneficial donor-versus-recipient natural killer (NK) cell-mediated alloreaction, we have conducted the first extensive analysis of the phenotypic and functional properties of NK cells after UCBT. NK cells from 25 patients with high-risk hematologic malignancies were compared with cells derived from both healthy adult and CB cells. We found that following UCBT, NK cells display not only some phenotypic features associated with maturity but also unique characteristics that make them fully functional against leukemic blasts. We propose that this full functionality of alloreactive donor-derived NK may drive graft-versus-leukemia reactions after UCBT.

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“…As T cells in the cord blood graft are antigen inexperienced, they contain few or no cytotoxic T cells directed against viral and bacterial peptides, which may cross-react with HLA alloantigens. The relative lack of post-thymic T cells and the T-cell naivety may be responsible for the lower-than expected frequency of severe GvHD, even in the setting of one or two HLA mismatches, and for the delayed recovery of T-cell function after UCBT [31][32][33] to the same degree as after haploidentical SCT. Lack of memory T cells in the graft (due to T-cell depletion in haploidentical and T-cell naivety in cord blood transplants) apparently permits the recovery of fully functional NK cells.…”

Section: Discussionmentioning

confidence: 99%

KIR-ligand incompatibility in the graft-versus-host direction improves outcomes after umbilical cord blood transplantation for acute leukemia

et al. 2009

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Donor killer cell immunoglobulin-like receptor (KIR)-ligand incompatibility is associated with decreased relapse incidence (RI) and improved leukemia-free survival (LFS) after haploidentical and HLA-mismatched unrelated hematopoietic stem cell transplantation. We assessed outcomes of 218 patients with acute myeloid leukemia (AML n ¼ 94) or acute lymphoblastic leukemia (n ¼ 124) in complete remission (CR) who had received a single-unit unrelated cord blood transplant (UCBT) from a KIR-ligand-compatible or -incompatible donor. Grafts were HLA-A, -B or -DRB1 matched (n ¼ 21) or mismatched (n ¼ 197). Patients and donors were categorized according to their degree of KIR-ligand compatibility in the graft-versus-host direction by determining whether or not they expressed HLA-C group 1 or 2, HLA-Bw4 or HLA-A3/-A11. Both HLA-C/-B KIR-ligand-and HLA-A-A3/-A11 KIR-ligand-incompatible UCBT showed a trend to improved LFS (P ¼ 0.09 and P ¼ 0.13, respectively). Sixty-nine donor-patient pairs were HLA-A, -B or -C KIR-ligand incompatible and 149 compatible. KIR-ligandincompatible UCBT showed improved LFS (hazards ratio ¼ 2.05, P ¼ 0.0016) and overall survival (OS) (hazards ratio ¼ 2.0, P ¼ 0.004) and decreased RI (hazards ratio ¼ 0.53, P ¼ 0.05). These results were more evident for AML transplant recipients (2-year LFS and RI with or without KIR-ligand incompatibility 73 versus 38% (P ¼ 0.012), and 5 versus 36% (P ¼ 0.005), respectively). UCBT for acute leukemia in CR from KIR-ligandincompatible donors is associated with decreased RI and improved LFS and OS.

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Similar Potential to Become Activated and Proliferate but Differential Kinetics and Profiles of Cytokine Production of Umbilical Cord Blood T Cells and Adult Blood Naive and Memory T Cells

Cited by 17 publications

References 27 publications

Regulation of Pulmonary Graft-versus-Host Disease by IL-26+CD26+CD4 T Lymphocytes

Regulation of Pulmonary Graft-versus-Host Disease by IL-26+CD26+CD4 T Lymphocytes

Fully functional NK cells after unrelated cord blood transplantation

KIR-ligand incompatibility in the graft-versus-host direction improves outcomes after umbilical cord blood transplantation for acute leukemia

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