Reconstitution of the T cell receptor repertoire after allogeneic bone marrow transplantation (allo-BMT) for SCID

1997 ◽  
Vol 56 (1-3) ◽  
pp. 38-39
Author(s):  
B Godthelp
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
T Cell Receptor ◽  
Marrow Transplantation ◽  
Allogeneic Bone Marrow Transplantation ◽  
Cell Receptor ◽  
Allogeneic Bone ◽  
Receptor Repertoire ◽  
T Cell Receptor Repertoire ◽  
Cell Receptor Repertoire

Organ-Specific T Cell Receptor Repertoire in Target Organs of Murine Graft-Versus-Host after Haploidentical Bone Marrow Transplantation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4859-4859
Author(s):  
Yue Wen Fu ◽  
De Pei Wu ◽  
Feng Chen ◽  
Yu Feng Feng ◽  
Wei Rong Chong ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Bone Marrow Transplantation ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Receptor Repertoire ◽  
Target Organs ◽  
T Cell Receptor Repertoire ◽  
Cell Receptor Repertoire

Abstract Objective Haploidentical bone marrow transplantation (Haploidentical-BMT) usually has high morbidity and mortality associated with the early complication of SCT and severe GVHD. GVHD-associated T-cell clones can be identified in GVHD-affected tissues. In our study, Murine CB6F1(H-2b/d, [male]) and C57BL/6(H-2b, [female]) haploidentical-BMT GVHD model was established and proved a novel method to study the characteristics of T cell receptor repertoire in target organs of murine GVHD and research the molecular characteristics of T cell receptor BV complementarity determining region3 (TCRBV CDR3) repertoires of these monoclonal T cells in liver, skin and ileum. Methods Murine haploidentical BMT model was established, RT-PCR was used to amplify 24 subfamily genes of TCRBV from liver, skin, ileum, spleen and kidney, PCR products were further analyzed by genescan to evaluate the clonality of BV subfamily and characteristics of CDR3, monoclonal bands were obtained thorough denaturation polyacrylamide gel electrophoresis and sequenced. A group of CDR3 molecules were obtained from GVHD-target tissues. Results GVHD occurred as early as days 14 and was proven by histology in liver, skin and ileum. After BMT, it emerged a number of new monoclonal and oligoclonal T cells in GVHD-target tissues, while kidney was not affected by GVHD and infiltrated by polycolnal T cell. 48 TCRBV CDR3 molecules of monoclonal T cells which obtained from liver, skin, ileum in different times after BMT have six C’-terminal motifs(TEVFF, DTQYF, YEQYF, A EQ (Y F/FF), QNTLY F, AE T L Y F)and use restricted JB genes(JB1.1, JB2.5, JB2.7, JB2.1, JB2.4, JB2.3). Conclusion Through murine haploidentical BMT GVHD model, TCRBV CDR3 was detected in GVHD-target tissues (liver, skin, ileum) and found that it emerged a number of monoclonal or oligoclonal T cells which associated with the development of GVHD and existed conserved CDR3 motifs.

scholarly journals Different T-cell receptor repertoires between lesions and peripheral blood in acute graft-versus-host disease after allogeneic bone marrow transplantation

Blood ◽  
1996 ◽  
Vol 87 (7) ◽  
pp. 3019-3026 ◽  
Author(s):  
K Kubo ◽  
K Yamanaka ◽  
H Kiyoi ◽  
H Fukutani ◽  
M Ito ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Bone Marrow Transplantation ◽  
T Cell ◽  
T Cell Receptor ◽  
Allogeneic Bone Marrow Transplantation ◽  
Cell Receptor ◽  
Allogeneic Bone ◽  
Graft Versus Host ◽  
Acute Graft

From the viewpoint of T-cell receptor (TCR) repertoire, we studied the role of T cells in acute graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (allo-BMT) from an HLA-identical sibling. By means of inverse polymerase chain reaction method and DNA sequencing, we analyzed TCR-alpha and -beta transcripts from GVHD lesions and peripheral blood (PB) in a patient with typical GVHD together with PB from donor. At the initial onset of GVHD, V alpha-7 and -19 subfamilies were oligoclonally expanded in the PB compared with those in the oral mucosal lesions. At the second onset, V alpha-2, and V beta-6 subfamilies were more frequently detected in the cutaneous lesion than in the PB. Some TCR transcripts were recurrently found either in the mucosal or cutaneous lesions (or in both) and not in the PB. Furthermore, some of recurrent TCR transcripts in the lesions shared V gene segments and common motifs of complementarity determining region-3. These findings suggested that T cells infiltrating the GVHD lesions recognized a limited kind of antigens presented by patient's tissues with GVHD, and that T-cell repertoire in the GVHD lesions was different from that in the PB.

Reconstitution of T-cell receptor repertoire diversity following T-cell depleted allogeneic bone marrow transplantation is related to hematopoietic chimerism

Blood ◽  
2000 ◽  
Vol 95 (1) ◽  
pp. 352-359 ◽  
Author(s):  
Catherine J. Wu ◽  
Antoinette Chillemi ◽  
Edwin P. Alyea ◽  
Enrica Orsini ◽  
Donna Neuberg ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
T Cell ◽  
T Cell Receptor ◽  
Allogeneic Bone Marrow Transplantation ◽  
Cell Receptor ◽  
Allogeneic Bone ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
Tcr Repertoire

CDR3 spectratyping was used to analyze the complexity of the T-cell repertoire and to define the mechanisms and kinetics of the reconstitution of T-cell immunity after allogeneic bone marrow transplantation (BMT). This method, which is based on polymerase chain reaction amplification of all CDR3 regions using the T-cell receptor (TCR) Vβ genes, was used to examine serial samples of peripheral blood lymphocytes from 11 adult patients with chronic myelogenous leukemia (CML) who underwent T-cell–depleted allogeneic BMT. In contrast to 10 normal donors who display highly diverse and polyclonal spectratypes, patient samples before and early after BMT revealed markedly skewed repertoires, consisting of absent, monoclonal, or oligoclonal profiles for the majority of Vβ subfamilies. To quantify changes in TCR repertoire over time, we established an 8-point scoring system for each Vβ subfamily. The mean complexity score for patient samples before transplant (130.8) was significantly lower than that for normal donors (183; P = 0.0007). TCR repertoire complexity was abnormal in all patients at 3 months after BMT (mean score = 87). Normalization of repertoire began in 4 patients at 6 months after BMT, but the majority of patients continued to display abnormal repertoires for up to 3 years after BMT. To determine whether the reconstituted T-cell repertoire was derived from the donor or recipient, unique microsatellite loci were examined to establish chimeric status. At 3 months after BMT, 7 patients demonstrated mixed chimerism; 4 had complete donor hematopoiesis (CDH). CDH strongly correlated with likelihood of restoration of T-cell repertoire complexity (P = 0.003). In contrast, patients who demonstrated persistence of recipient hematopoiesis failed to reconstitute a diverse TCR repertoire. These findings suggest that the reconstitution of a normal T-cell repertoire from T-cell progenitors in adults is influenced by interactions between recipient and donor hematopoietic cells. (Blood. 2000;95: 352-359)

Reconstitution of T-cell receptor repertoire diversity following T-cell depleted allogeneic bone marrow transplantation is related to hematopoietic chimerism

Blood ◽  
2000 ◽  
Vol 95 (1) ◽  
pp. 352-359 ◽  
Author(s):  
Catherine J. Wu ◽  
Antoinette Chillemi ◽  
Edwin P. Alyea ◽  
Enrica Orsini ◽  
Donna Neuberg ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
T Cell ◽  
T Cell Receptor ◽  
Allogeneic Bone Marrow Transplantation ◽  
Cell Receptor ◽  
Allogeneic Bone ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
Tcr Repertoire

Abstract CDR3 spectratyping was used to analyze the complexity of the T-cell repertoire and to define the mechanisms and kinetics of the reconstitution of T-cell immunity after allogeneic bone marrow transplantation (BMT). This method, which is based on polymerase chain reaction amplification of all CDR3 regions using the T-cell receptor (TCR) Vβ genes, was used to examine serial samples of peripheral blood lymphocytes from 11 adult patients with chronic myelogenous leukemia (CML) who underwent T-cell–depleted allogeneic BMT. In contrast to 10 normal donors who display highly diverse and polyclonal spectratypes, patient samples before and early after BMT revealed markedly skewed repertoires, consisting of absent, monoclonal, or oligoclonal profiles for the majority of Vβ subfamilies. To quantify changes in TCR repertoire over time, we established an 8-point scoring system for each Vβ subfamily. The mean complexity score for patient samples before transplant (130.8) was significantly lower than that for normal donors (183; P = 0.0007). TCR repertoire complexity was abnormal in all patients at 3 months after BMT (mean score = 87). Normalization of repertoire began in 4 patients at 6 months after BMT, but the majority of patients continued to display abnormal repertoires for up to 3 years after BMT. To determine whether the reconstituted T-cell repertoire was derived from the donor or recipient, unique microsatellite loci were examined to establish chimeric status. At 3 months after BMT, 7 patients demonstrated mixed chimerism; 4 had complete donor hematopoiesis (CDH). CDH strongly correlated with likelihood of restoration of T-cell repertoire complexity (P = 0.003). In contrast, patients who demonstrated persistence of recipient hematopoiesis failed to reconstitute a diverse TCR repertoire. These findings suggest that the reconstitution of a normal T-cell repertoire from T-cell progenitors in adults is influenced by interactions between recipient and donor hematopoietic cells. (Blood. 2000;95: 352-359)

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