T-Cell Receptor Variable Gene Analysis of Renal Allograft-Infiltrating Cells in Biopsy Specimens Using a Nonradioisotopic Micromethod1

Obata, Fumiya; Kumano, Kazuo; Endo, Tadao; Takeuchi, Yasuo; Ohkubo, M; Tsunoda-iizuka, Misao

doi:10.1097/00007890-199811270-00022

Cited by 7 publications

(8 citation statements)

References 8 publications

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“…Owens et al (25) suggested that the establishment of short-term stable renal allograft function (1 year posttransplantation) requires the deletion of certain T cells from peripheral blood. Whereas many studies described TCR usage during graft rejection in humans (14,(26)(27)(28)(29), to our knowledge, no studies on TCR usage in long-term functioning kidney transplants have hitherto been reported.…”

Section: Discussionmentioning

confidence: 98%

Evaluation of T-Cell Receptor Repertoires in Patients with Long-Term Renal Allograft Survival

Álvarez

Opelz

Giraldo

et al. 2005

American Journal of Transplantation

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The mechanisms underlying long-term acceptance of kidney allografts in humans under minimal or no maintenance immunosuppression are poorly understood. We analyzed the T-cell receptor (TCR) repertoires in circulating T cells of patients with long-term (≥9 years) renal allograft survival with (LTS-IS) and without immunosuppression (LTS-NoIS). T cells of LTS patients exhibited strongly altered TCR Vß usage, including an increased frequency of oligoclonality and a decreased frequency of polyclonality. All 3 LTS-NoIS and 12 of 16 LTS-IS patients demonstrated oligoclonality in at least three or more TCR Vß families, and the frequency of oligoclonality in these patients was significantly higher as compared to patients with well-functioning grafts at 3 years (p < 0.005 both), an uncomplicated course during the first year (p < 0.0001, both), acute rejection (p < 0.0001, both), chronic allograft nephropathy at 7 (p < 0.0001, both) or 13 years (p < 0.0001, both), dialysis patients (p < 0.0001, both) or healthy controls (p < 0.0001, both). In contrast to LTS patients, all other studied patient groups exhibited a polyclonal TCR repertoire. Our data indicate that TCR alteration is a common feature of long-term allograft outcome, which might be explained by clonal deletion, exhaustion of alloreactive T cells or predominant expression of particular T-cell subpopulations, such as regulatory T cells.

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Section: Discussionmentioning

confidence: 98%

Evaluation of T-Cell Receptor Repertoires in Patients with Long-Term Renal Allograft Survival

Álvarez

Opelz

Giraldo

et al. 2005

American Journal of Transplantation

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“…Obata et al demonstrated the skew of TCR repertoires in T cells infiltrating into the renal allografts by hybridization technique (24). Hall et al demonstrated the skew of TCR repertoires in T cells infiltrating into human renal allografts by semiquantitative PCR after in vitro culture (13).…”

Section: Relationship Between Clonal T-cell Expansion and The Functiomentioning

confidence: 99%

“…Quantitative methods, including monoclonal antibodies (25), PCR (18,26), and a hybridization technique (24), have been used for the analysis of TCR repertoires. Clonality of T cells has been analyzed by Southern blot hybridization (27), CDR3 length analysis (15), and single-strand conformation polymorphism (28).…”

Section: Relationship Between Clonal T-cell Expansion and The Functiomentioning

confidence: 99%

Skew in T-cell receptor usage and clonal T-cell expansion in patients with chronic rejection of transplanted kidneys

et al. 2003

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“…The majority of studies of TcR gene usage in rejection focus on TRBV family repertoire or on alloreactive clones in vitro. (10)(11)(12)(39)(40)(41). In chronic rejection a restricted usage of TRBV has been shown by spectratyping and 'immunoscope' analysis (13).…”

Section: Discussionmentioning

confidence: 99%

“…TRBV repertoires reflect the diversity of the T-cell repertoire used by alloreactive T cells to recognize foreign tissue in transplantation. Altered TRBV repertoires have been described in studies of allograft rejection (10)(11)(12). Restricted TRBV repertoires were observed in patients with both acute and progressive chronic rejection (10).…”

Section: Introductionmentioning

confidence: 99%

Matching T-Cell Receptors Identified in Renal Biopsies and Urine at the Time of Acute Rejection in Pediatric Renal Transplant Patients

Zhang

Walters

et al. 2004

American Journal of Transplantation

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Urinary monitoring of kidney allograft function has been used for many years. More recently, molecular identification of cytotoxic T-cell products has been used as a diagnostic tool in acute rejection. Monitoring of T-cell infiltrates by analysis of the T-cell receptor (TcR) gene usage has been performed on biopsies with acute and chronic rejection, but not on urine samples. The aim of this study was to identify and compare TRBV gene usage assessing the CDR3 (Complementarity Determining Region 3) length distribution and sequence in urine and biopsies of pediatric renal allograft patients at the time of acute rejection and compare them with peripheral blood. We studied four pediatric renal transplant recipients with acute cellular rejection. We identified restricted and matched TRBV CDR3 spectratypes with overexpressed TRBV families and show identical, clonally expanded TRBV CDR3 sequences in all four patients present in the urine and renal allograft. We demonstrate that urinary monitoring can detect graft-infiltrating lymphocytes in acute rejection and may have a role in the monitoring of renal transplants.

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T-Cell Receptor Variable Gene Analysis of Renal Allograft-Infiltrating Cells in Biopsy Specimens Using a Nonradioisotopic Micromethod1

Abstract: We have established a powerful method for analyzing RAIT clonality, which is especially useful for monitoring RAIT dynamics after immunosuppression therapy.

Cited by 7 publications

References 8 publications

Evaluation of T-Cell Receptor Repertoires in Patients with Long-Term Renal Allograft Survival

Evaluation of T-Cell Receptor Repertoires in Patients with Long-Term Renal Allograft Survival

Skew in T-cell receptor usage and clonal T-cell expansion in patients with chronic rejection of transplanted kidneys

Matching T-Cell Receptors Identified in Renal Biopsies and Urine at the Time of Acute Rejection in Pediatric Renal Transplant Patients

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