Evidence map›Paper›PMID 26287728›Full record

ArticlePloS one2015

Clonal CD8+ T Cell Persistence and Variable Gene Usage Bias in a Human Transplanted Hand.

Joseph Y Kim, Arumugam Balamurugan, Kodi Azari, Christian Hofmann, Hwee L Ng, Elaine F Reed, Suzanne McDiarmid, Otto O Yang

Erratum issuedAbstract readCase Reports
PubMed Full text at PMC Publisher
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Joseph Y KimDivision of Infectious Diseases, Department of Medicine, Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America; Department of Microbiology, Immunology, and Molecular Genetics, Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
Arumugam BalamuruganDivision of Infectious Diseases, Department of Medicine, Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
Kodi AzariDepartment of Orthopaedic Surgery, Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
Christian HofmannDivision of Infectious Diseases, Department of Medicine, Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
Hwee L NgDivision of Infectious Diseases, Department of Medicine, Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
Elaine F ReedDepartment of Pathology and Laboratory Medicine, Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America; UCLA Immunogenetics Center, Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
Suzanne McDiarmidDivision of Gastroenterology, Department of Pediatrics, Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
Otto O YangDivision of Infectious Diseases, Department of Medicine, Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America; Department of Microbiology, Immunology, and Molecular Genetics, Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.

Funding

UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0M
TRANSLATIONAL AIDS AND VIRAL PATHOGENESIS TRAINING (51)T32AI089398 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI YANG, OTTO O · 2010 to 2017
$1.6M
NCATS NIH HHS UL1 TR000124NCATS NIH HHS UL1TR000124NIAID NIH HHS T32 AI089398
6 · The paper itself

Abstract

Immune prophylaxis and treatment of transplanted tissue rejection act indiscriminately, risking serious infections and malignancies. Although animal data suggest that cellular immune responses causing rejection may be rather narrow and predictable based on genetic background, there are only limited data regarding the clonal breadth of anti-donor responses in humans after allogeneic organ transplantation. We evaluated the graft-infiltrating CD8+ T lymphocytes in skin punch biopsies of a transplanted hand over 178 days. Profiling of T cell receptor (TCR) variable gene usage and size distribution of the infiltrating cells revealed marked skewing of the TCR repertoire indicating oligoclonality, but relatively normal distributions in the blood. Although sampling limitation prevented complete assessment of the TCR repertoire, sequencing further identified 11 TCR clonal expansions that persisted through varying degrees of clinical rejection and immunosuppressive therapy. These 11 clones were limited to three TCR beta chain variable (BV) gene families. Overall, these data indicate significant oligoclonality and likely restricted BV gene usage of alloreactive CD8+ T lymphocytes, and suggest that changes in rejection status are more due to varying regulation of their activity or number rather than shifts in the clonal populations in the transplanted organ. Given that controlled animal models produce predictable BV usage in T lymphocytes mediating rejection, understanding the determinants of TCR gene usage associated with rejection in humans may have application in specifically targeted immunotherapy.

Indexed as

Hand TransplantationAdultAmino Acid SequenceAnimalsCD8-Positive T-LymphocytesFemaleGenes, T-Cell ReceptorGenetic VariationGraft RejectionHumansModels, ImmunologicalMolecular Sequence DataSequence Homology, Amino AcidSkinTime Factors

Identifiers

PMID26287728
PMCPMC4546120

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.