Evidence map›Paper›PMID 19841178›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2009

Regulatory T cell (Treg) subsets return in patients with refractory lupus following stem cell transplantation, and TGF-beta-producing CD8+ Treg cells are associated with immunological remission of lupus.

Li Zhang, Anne M Bertucci, Rosalind Ramsey-Goldman, Richard K Burt, Syamal K Datta

Open access · bronzeAbstract read
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
93citing papers in PubMed, 2 pooled it
4.8field-weighted citation impact, top 4% of its field
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

93 citing papers in PubMed, 2 syntheses or guidelines pooled it, 163 citations in OpenAlex.

  1. Pooled it
  2. Guideline
  3. Trial
  4. Trial
  5. Article
  6. Review
  7. Review
  8. Review
  9. Article
  10. Article
  11. Stem cell-based therapy for systemic lupus erythematous.Journal of translational autoimmunity · 2024
    Review
  12. Article
  13. Article
  14. Peptide-based immunotherapy in lupus: Where are we now?Rheumatology and immunology research · 2023
    Review
  15. Article
  16. CD8Immunity · 2023
    Article
  17. Article
  18. Review
  19. Stem Cell Therapy in Lupus.Rheumatology and immunology research · 2022
    Review
  20. Article

33 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 3 institutions in 3 countries.

Li ZhangDivision of Rheumatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Anne M Bertucci
Rosalind Ramsey-Goldman
Richard K Burt
Syamal K Datta
Center for Rheumatology · USNorthwestern University · USOSE Immunotherapeutics (France) · FR

Funding

MULTIDISCIPLINARY CLINICAL AND TRANSLATIONAL SCIENCE (MCTS) PROGRAM (UL1)UL1RR025741 · NCRR · NORTHWESTERN UNIVERSITY AT CHICAGO · PI GREENLAND, PHILIP · 2008 to 2011
$24.7M
MECHANISM OF AUTOIMMUNE RESPONSE IN HUMAN LUPUSR37AR039157 · NIAMS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI DATTA, SYAMAL K · 2000 to 2009
$2.8M
SUPERANTIGEN INTERACTIONS WITH MHC CLASS II ANTIGENSP60AR030692 · NIAMS · NORTHWESTERN UNIVERSITY · PI POPE, RICHARD M. · 1986 to 2001
$2.1M
PATHOGENIC ANTIDNA AUTOANTIAB REGULATION IN LUPUSR01AR039157 · NIAMS · TUFTS MEDICAL CENTER · PI DATTA, SYAMAL K · 1989 to 1999
–
NCRR NIH HHS UL1 RR025741NIAMS NIH HHS P60 AR030692NIAMS NIH HHS P60 AR30692NIAMS NIH HHS R01 AR039157NIAMS NIH HHS R01 AR39157NIAMS NIH HHS R37 AR039157
6 · The paper itself

Abstract

Compared with conventional drug therapy, autologous hemopoietic stem cell transplantation (HSCT) can induce very-long-term remission in refractory lupus patients. Herein, we show that in posttransplant patients, both CD4(+)CD25(high)FoxP3(+) and an unusual CD8(+)FoxP3(+) Treg subset return to levels seen in normal subjects; accompanied by almost complete inhibition of pathogenic T cell response to critical peptide autoepitopes from histones in nucleosomes, the major lupus autoantigen from apoptotic cells. In addition to a stably sustained elevation of FoxP3, posttransplant CD8 T cells also maintained markedly higher expression levels of latency-associated peptide (LAP), CD103, PD-1, PD-L1, and CTLA-4, as compared with pretransplant CD8 T cells that were identically treated by a one-time activation and rest in short-term culture. The posttransplant CD8 regulatory T cells (Treg) have autoantigen-specific and nonspecific suppressive activity, which is contact independent and predominantly TGF-beta dependent. By contrast, the pretransplant CD8 T cells have helper activity, which is cell contact dependent. Although CD4(+)CD25(high) Treg cells return during clinical remission of conventional drug-treated lupus, the posttransplant patient's CD8 Treg cells are considerably more potent, and they are absent in drug-treated patients in whom CD4 T cell autoreactivity to nucleosomal epitopes persists even during clinical remission. Therefore, unlike conventional drug therapy, hemopoietic stem cell transplantation generates a newly differentiated population of LAP(high)CD103(high) CD8(TGF-beta) Treg cells, which repairs the Treg deficiency in human lupus to maintain patients in true immunological remission.

Indexed as

Hematopoietic Stem Cell TransplantationAdolescentAdultAntigens, CDApoptosis Regulatory ProteinsB7-H1 AntigenCD8-Positive T-LymphocytesCTLA-4 AntigenFemaleHumansIntegrin alpha ChainsInterferon-gammaInterleukin-13Lupus Erythematosus, SystemicMaleMiddle Agedalpha E integrinsAntigens, CDApoptosis Regulatory ProteinsB7-H1 AntigenCD274 protein, humanCTLA-4 AntigenCTLA4 protein, humanIntegrin alpha ChainsInterferon-gammaInterleukin-13NucleosomesPDCD1 protein, humanProgrammed Cell Death 1 ReceptorTransforming Growth Factor beta

Identifiers

PMID19841178
PMCPMC2784684
OpenAlexW2119652081

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.