Evidence map›Paper›PMID 38607279›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2024

Disruption of IFNγ, GZMB, PRF1, or LYST Results in Reduced Suppressive Function in Human CD8+ T Cells.

Chakrapani Vemulawada, Pranav S Renavikar, Michael P Crawford, Scott Steward-Tharp, Nitin J Karandikar

Open access · greenAbstract read
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
2.4field-weighted citation impact, top 11% 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

13 citing papers in PubMed, 10 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. CD4European journal of immunology · 2026
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Myelin-reactive CD8Journal of neuroinflammation · 2025
    Article
  11. Frontiers in oncology · 2025
    Article
  12. Article
  13. 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

5 authors at 2 institutions in 1 country.

Chakrapani VemulawadaDepartment of Pathology, University of Iowa Health Care, Iowa City.ORCID 0000-0002-6714-7766
Pranav S RenavikarDepartment of Pathology, University of Iowa Health Care, Iowa City.ORCID 0009-0006-4226-2633
Michael P CrawfordDepartment of Pathology, University of Iowa Health Care, Iowa City.
Scott Steward-TharpDepartment of Pathology, University of Iowa Health Care, Iowa City.ORCID 0000-0002-5865-4539
Nitin J KarandikarDepartment of Pathology, University of Iowa Health Care, Iowa City.ORCID 0000-0002-6867-6950
Veterans Health Administration · USUniversity of Iowa Health Care · US

Funding

Immune Dysregulation During Multiple Sclerosis RelapseR01AI121567 · NIAID · UNIVERSITY OF IOWA · PI KARANDIKAR, NITIN J · 2016 to 2020
$3.8M
Effector-Regulator Immune Interactions During Autoimmune Demyelinating DiseaseI01CX002319 · VA · IOWA CITY VA MEDICAL CENTER · PI NITIN J KARANDIKAR · 2022 to 2026
–
CSRD VA I01 CX002319NIAID NIH HHS R01 AI121567
6 · The paper itself

Abstract

An imbalance between proinflammatory and regulatory processes underlies autoimmune disease pathogenesis. We have shown that acute relapses of multiple sclerosis are characterized by a deficit in the immune suppressive ability of CD8+ T cells. These cells play an important immune regulatory role, mediated in part through cytotoxicity (perforin [PRF]/granzyme [GZM]) and IFNγ secretion. In this study, we further investigated the importance of IFNγ-, GZMB-, PRF1-, and LYST-associated pathways in CD8+ T cell-mediated suppression. Using the CRISPR-Cas9 ribonucleoprotein transfection system, we first optimized efficient gene knockout while maintaining high viability in primary bulk human CD8+ T cells. Knockout was confirmed through quantitative real-time PCR assays in all cases, combined with flow cytometry where appropriate, as well as confirmation of insertions and/or deletions at genomic target sites. We observed that the knockout of IFNγ, GZMB, PRF1, or LYST, but not the knockout of IL4 or IL5, resulted in significantly diminished in vitro suppressive ability in these cells. Collectively, these results reveal a pivotal role for these pathways in CD8+ T cell-mediated immune suppression and provide important insights into the biology of human CD8+ T cell-mediated suppression that could be targeted for immunotherapeutic intervention.

Indexed as

CD8-Positive T-LymphocytesGranzymesInterferon-gammaPerforinCells, CulturedCRISPR-Cas SystemsGene Knockout TechniquesHumansMultiple SclerosisGranzymesGZMB protein, humanIFNG protein, humanInterferon-gammaPerforinPRF1 protein, human

Identifiers

PMID38607279
PMCPMC11105984
OpenAlexW4394750106

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.