A novel approach for the analysis of T-cell reconstitution by using a T-cell receptor β-based oligonucleotide microarray in hematopoietic stem cell transplantation

2007 ◽  
Vol 35 (5) ◽  
pp. 831-841 ◽  
Author(s):  
Xiaohua Chen ◽  
Gregory A. Hale ◽  
Geoffrey A.M. Neale ◽  
James Knowles ◽  
Raymond C. Barfield ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Hematopoietic Stem ◽  
T Cell Reconstitution ◽  
Novel Approach

scholarly journals Genetic T-cell receptor diversity at 1 year following allogeneic hematopoietic stem cell transplantation

Leukemia ◽  
2019 ◽  
Vol 34 (5) ◽  
pp. 1422-1432 ◽  
Author(s):  
Stéphane Buhler ◽  
Florence Bettens ◽  
Carole Dantin ◽  
Sylvie Ferrari-Lacraz ◽  
Marc Ansari ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Hematopoietic Stem

Prediction of T-cell reconstitution by assessment of T-cell receptor excision circle before allogeneic hematopoietic stem cell transplantation in pediatric patients

Blood ◽  
2005 ◽  
Vol 105 (2) ◽  
pp. 886-893 ◽  
Author(s):  
Xiaohua Chen ◽  
Raymond Barfield ◽  
Ely Benaim ◽  
Wing Leung ◽  
James Knowles ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Hematopoietic Stem ◽  
Thymic Function ◽  
T Cell Reconstitution

Abstract The extent and rapidity with which T cells are regenerated from graft-derived precursor cells directly influences the incidence of infection and the T-cell–based graft-versus-tumor effect. Measurement of T-cell receptor excision circles (TRECs) in peripheral blood is a means of quantifying recent thymic T-cell production and has been used after transplantation in many studies to estimate thymus-dependent T-cell reconstitution. We hypothesized that the quality of thymic function before transplantation affects thymus-dependent T-cell reconstitution after transplantation. We used real-time polymerase chain reaction (PCR) to quantify signal-joint TRECs (sjTRECs) before and after transplantation. T-cell reconstitution was evaluated by T-cell receptor β (TCRβ) CDR3 size spectratyping. We tested 77 healthy sibling donors and 244 samples from 26 pediatric recipients of allogeneic hematopoietic stem cell transplantation (AHSCT). Blood from the healthy donors contained 1200 to 155 000 sjTREC copies/mL blood. Patients who had greater than 1200 copies/mL blood before transplantation showed early recovery of sjTREC numbers and TCRβ repertoire diversity. In contrast, patients who had fewer than 1200 copies/mL blood before transplantation demonstrated significantly slower restoration of thymus-dependent T cells. We conclude that the rate of reconstitution of thymus-dependent T cells is dependent on the competence of thymic function in the recipients before transplantation. Therefore, pretransplantation measurement of sjTREC may provide an important tool for predicting thymus-dependent T-cell reconstitution after transplantation.

Long-term T-cell reconstitution after hematopoietic stem-cell transplantation in primary T-cell–immunodeficient patients is associated with myeloid chimerism and possibly the primary disease phenotype

Blood ◽  
2007 ◽  
Vol 109 (10) ◽  
pp. 4575-4581 ◽  
Author(s):  
Marina Cavazzana-Calvo ◽  
Frédérique Carlier ◽  
Françoise Le Deist ◽  
Estelle Morillon ◽  
Pierre Taupin ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Cell Receptor ◽  
Hematopoietic Stem ◽  
T Cell Reconstitution

Abstract We studied T-cell reconstitution in 31 primary T-cell–immunodeficient patients who had undergone hematopoietic stem-cell transplantation (HSCT) over 10 years previously. In 19 patients, there was no evidence of myeloid chimerism because little or no myeloablation had been performed. Given this context, we sought factors associated with good long-term T-cell reconstitution. We found that all patients having undergone full myeloablation had donor myeloid cells and persistent thymopoiesis, as evidenced by the presence of naive T cells carrying T-cell receptor excision circles (TRECs). In 9 patients with host myeloid chimerism, sustained thymic output was also observed and appeared to be associated with γc deficiency. It is therefore possible that the complete absence of thymic progenitors characterizing this condition created a more favorable environment for thymic seeding by a population of early progenitor cells with the potential for self-renewal, thus enabling long-term (> 10 years) T-cell production.

scholarly journals Alpha/Beta T-Cell Depleted Grafts as an Immunological Booster to Treat Graft Failure after Hematopoietic Stem Cell Transplantation with HLA-Matched Related and Unrelated Donors

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
E. Rådestad ◽  
H. Wikell ◽  
M. Engström ◽  
E. Watz ◽  
B. Sundberg ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Hematopoietic Stem ◽  
Unrelated Donors

Allogeneic hematopoietic stem cell transplantation is associated with several complications and risk factors, for example, graft versus host disease (GVHD), viral infections, relapse, and graft rejection. While high levels of CD3+ cells in grafts can contribute to GVHD, they also promote the graft versus leukemia (GVL) effect. Infusions of extra lymphocytes from the original stem cell donor can be used as a treatment after transplantation for relapse or poor immune reconstitution but also they increase the risk for GVHD. In peripheral blood, 95% of T-cells express theαβT-cell receptor and the remaining T-cells express theγδT-cell receptor. AsαβT-cells are the primary mediators of GVHD, depleting them from the graft should reduce this risk. In this pilot study, five patients transplanted with HLA-matched related and unrelated donors were treated withαβT-cell depleted stem cell boosts. The majority ofγδT-cells in the grafts expressedVδ2and/orVγ9. Most patients receivingαβ-depleted stem cell boosts increased their levels of white blood cells, platelets, and/or granulocytes 30 days after infusion. No signs of GVHD or other side effects were detected. A larger pool of patients with longer follow-up time is needed to confirm the data in this study.

scholarly journals Successful hematopoietic stem cell transplantation in a patient with a novel mutation in coronin 1A

2019 ◽  
Vol 6 (2) ◽  
pp. 52-60
Author(s):  
Adi Ovadia ◽  
Vy Hong-Diep Kim ◽  
Brenda Reid ◽  
Harjit Dadi ◽  
Anne Pham-Huy ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
T Cell Receptor ◽  
Novel Mutation ◽  
Cell Receptor ◽  
Hematopoietic Stem

Introduction: Coronin 1A is part of a family of highly conserved actin regulatory proteins with key roles in T cell homeostasis and T cell receptor signaling. Null mutations in coronin 1A result in severe combined immunodeficiency, whereas hypomorphic mutations have been associated with a somewhat milder immunological phenotype. Nevertheless, all patients described so far have markedly reduced naïve peripheral T cells, impaired T cell responses to mitogens, and limited T cell receptor diversity. Interestingly, despite poor thymic output, thymus architecture appears normal. To date, only 2 cases of hematopoietic stem cell transplantation (HSCT) have been reported in coronin 1A deficiency. Aim: To describe the identification, transplantation course, and long term outcome of a Canadian Inuit patient diagnosed with coronin 1A deficiency. Methods: Patient chart review was performed in accordance with institutional research ethics approval. A combination of immunological investigations and molecular genetic analyses were utilized to identify a novel mutation in the tryptophan-aspartate repeat region of coronin 1A. Based on the patient’s profound T cell dysfunction, the decision was made to proceed with HSCT. Results: The patient presented with a history of recurrent urinary tract infections, otitis media, and developmental delay involving poor axial and peripheral muscle tone. Axillary lymphadenopathy was noted and subsequent thymus biopsy revealed aberrant CD7+ T cell deficiency. Lymphocyte responses to mitogens and T cell receptor excision circle levels were markedly reduced, consistent with the diagnosis of severe combined immunodeficiency. Whole exome sequencing and Sanger confirmation revealed a novel mutation in coronin 1A. HSCT using a HLA-matched unrelated donor resulted in long term engraftment and solid immune reconstitution. Conclusion: Very few patients with coronin 1A deficiency have been described to date, making it difficult to evaluate its natural history and management. Here, we describe the presentation, identification, transplantation, and outcome in our patient. Statement of novelty: We describe the successful hematopoietic stem cell transplantation course and outcome in a patient with a novel mutation in coronin 1A.

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