Evidence map›Paper›PMID 21084663›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2010

CD8+ T cells negatively regulate IL-4-dependent, IgG1-dominant posttransplant alloantibody production.

Jason M Zimmerer, Thomas A Pham, Virginia M Sanders, Ginny L Bumgardner

Open access · bronzeAbstract read
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
0.2field-weighted citation impact, top 41% 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

21 citing papers in PubMed, 25 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Antibody-suppressor CXCR5American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2022
    Article
  8. CXCR5Journal of immunology (Baltimore, Md. : 1950) · 2021
    Review
  9. Article
  10. Experimental modeling of desensitization: What have we learned about preventing AMR?American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2020
    Review
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Immunological aspects of liver cell transplantation.World journal of transplantation · 2016
    Review
  18. Article
  19. Critical role of NKT cells in posttransplant alloantibody production.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2014
    Article
  20. Alloprimed CD8(+) T cells regulate alloantibody and eliminate alloprimed B cells through perforin- and FasL-dependent mechanisms.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2014
    Article
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

4 authors at 2 institutions in 1 country.

Jason M ZimmererDepartment of Surgery, Comprehensive Transplant Center, Ohio State University Medical Center, Columbus, OH 43210, USA.
Thomas A Pham
Virginia M Sanders
Ginny L Bumgardner
The Ohio State University · USThe Ohio State University Wexner Medical Center · US

Funding

Pre-Conditioning Pancreatic Islets for TransplantationR21DK072262 · NIDDK · OHIO STATE UNIVERSITY · PI BUMGARDNER, GINNY L · 2005 to 2006
$406k
CD8+ T cell regulation of alloantibody production following transplantationF32DK082148 · NIDDK · OHIO STATE UNIVERSITY · PI ZIMMERER, JASON M. · 2009 to 2010
$97k
NIDDK NIH HHS DK072262NIDDK NIH HHS F32 DK082148NIDDK NIH HHS R21 DK072262
6 · The paper itself

Abstract

We have previously reported that CD8(+) T cells significantly influence Ab production based on the observation that posttransplant alloantibody levels in CD8-deficient murine hepatocyte transplant recipients are markedly enhanced. However, the precise mechanisms contributing to enhanced alloantibody production in the absence of CD8(+) T cells is not understood. We hypothesized that alloactivated CD8(+) T cells inhibit Ab production by skewing toward a proinflammatory cytokine profile, whereas when these cells are absent, an anti-inflammatory cytokine profile shifts the alloimmune response toward alloantibody production. To investigate this possibility, alloantibody isotype profiles were examined in CD8-deficient and wild-type hepatocyte recipients. We found that IgG1 (IL-4-dependent isotype) was the dominant alloantibody isotype in wild-type recipients as well as in CD8-deficient recipients, although the amount of alloantibody in the latter group was substantially higher. Utilizing real-time PCR we found that CD4(+) T cells from wild-type recipients significantly upregulated IFN-γ but not IL-4 mRNA. In contrast, in the absence of CD8(+) T cells, CD4(+) T cells switched to significantly upregulate IL-4 mRNA, while IFN-γ was downregulated. IL-4 knockout mice do not produce any posttransplant alloantibody. However, adoptive transfer of wild-type CD4(+) T cells into CD8-depleted IL-4 knockout mice restores high alloantibody levels observed in CD8-depleted wild-type recipients. This suggests that IL-4-producing CD4(+) T cells are critical for posttransplant alloantibody production. Additionally, this CD8-mediated regulation of posttransplant alloantibody production is IFN-γ-dependent. Further elucidation of the mechanisms by which CD8(+) T cells influence Ab production will significantly contribute to development of therapies to manipulate humoral responses to Ag.

Indexed as

Adoptive TransferAnimalsAntibody FormationCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesGraft RejectionHepatocytesImmunoglobulin GInterferon-gammaInterleukin-4IsoantibodiesMiceMice, KnockoutTransplantation, HomologousUp-RegulationImmunoglobulin GInterferon-gammaInterleukin-4Isoantibodies

Identifiers

PMID21084663
PMCPMC3010751
OpenAlexW2112374237

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.