Evidence map›Paper›PMID 34991160›Full record

ArticleBlood advances2022

Hypermethylation at the CXCR5 gene locus limits trafficking potential of CD8+ T cells into B-cell follicles during HIV-1 infection.

Funsho J Ogunshola, Werner Smidt, Anneta F Naidoo, Thandeka Nkosi, Thandekile Ngubane, Trevor Khaba, Omolara O Baiyegunhi, Bongiwe Mahlobo, Sam Rasehlo, Namani Ngema and 8 more

Open access · goldAbstract read
In one paragraph

Article in Blood advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.9field-weighted citation impact, top 25% 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

8 citing papers in PubMed, 12 citations in OpenAlex.

  1. Review
  2. IBA-1Research square · 2026
    Article
  3. HIV reservoirs in lymphomagenesis: hidden driver in the era of viral suppression?Microbiology and molecular biology reviews : MMBR · 2025
    Review
  4. Review
  5. Article
  6. Article
  7. Article
  8. Role of CXCR5Frontiers in microbiology · 2022
    Review
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

18 authors at 4 institutions in 3 countries.

Funsho J OgunsholaAfrica Health Research Institute, Durban, South Africa.
Werner SmidtAfrica Health Research Institute, Durban, South Africa.ORCID 0000-0002-6197-4103
Anneta F NaidooHIV Vaccine Trial Network, Cape Town, South Africa.
Thandeka NkosiAfrica Health Research Institute, Durban, South Africa.
Thandekile NgubanePrince Mshiyeni Memorial Hospital, Durban, South Africa.
Trevor KhabaHIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
Omolara O BaiyegunhiAfrica Health Research Institute, Durban, South Africa.ORCID 0000-0001-8361-5534
Bongiwe MahloboAfrica Health Research Institute, Durban, South Africa.
Sam RasehloAfrica Health Research Institute, Durban, South Africa.ORCID 0000-0002-2324-8362
Namani NgemaHIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
Ismail JajbhayPrince Mshiyeni Memorial Hospital, Durban, South Africa.
Krista L DongRagon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA.ORCID 0000-0002-2038-3518
Veron RamsuranKwaZulu-Natal Research Innovation and Sequencing Platform, University of KwaZulu-Natal, Durban, South Africa.ORCID 0000-0003-1590-9893
Johan PansegrouwPrince Mshiyeni Memorial Hospital, Durban, South Africa.
Thumbi Ndung'uAfrica Health Research Institute, Durban, South Africa.
Bruce D WalkerRagon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA.ORCID 0000-0001-6122-9245
Tulio de OliveriaKwaZulu-Natal Research Innovation and Sequencing Platform, University of KwaZulu-Natal, Durban, South Africa.ORCID 0000-0002-3027-5254
Zaza M NdhlovuAfrica Health Research Institute, Durban, South Africa.ORCID 0000-0002-2708-3315
Africa Health Research Institute · ZARagon Institute of MGH, MIT and Harvard · USUniversity of KwaZulu-Natal · ZAHoward Hughes Medical Institute · US

Funding

Pathogenesis of Clade C HIV InfectionR37AI067073 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI WALKER, BRUCE D · 2011 to 2020
$6.6M
Epigenetic Control of CD8 T-Cell Differentiation in Human Lymph NodesR01AI145305 · NIAID · KWAZULU-NATAL RESEARCH INSTITUTE TB-HIV · PI NDHLOVU, ZAZA MTINE · 2019 to 2023
$715k
NIAID NIH HHS R01 AI145305NIAID NIH HHS R37 AI067073Wellcome Trust
6 · The paper itself

Abstract

CD8+ T cells play an important role in HIV control. However, in human lymph nodes (LNs), only a small subset of CD8+ T cells express CXCR5, the chemokine receptor required for cell migration into B-cell follicles, which are major sanctuaries for HIV persistence in individuals on therapy. Here, we investigate the impact of HIV infection on follicular CD8+ T cell (fCD8) frequencies, trafficking patterns, and CXCR5 regulation. We show that, although HIV infection results in a marginal increase in fCD8s in LNs, the majority of HIV-specific CD8+ T cells are CXCR5- (non-fCD8s) (P < .003). Mechanistic investigations using Assay for Transposase-Accessible Chromatin using sequencing showed that non-fCD8s have closed chromatin at the CXCR5 transcriptional start site (TSS). DNA bisulfite sequencing identified DNA hypermethylation at the CXCR5 TSS as the most probable cause of closed chromatin. Transcriptional factor footprint analysis revealed enrichment of transforming growth factors (TGFs) at the TSS of fCD8s. In vitro stimulation of non-fCD8s with recombinant TGF-β resulted in a significant increase in CXCR5 expression (fCD8s). Thus, this study identifies TGF-β signaling as a viable strategy for increasing fCD8 frequencies in follicular areas of the LN where they are needed to eliminate HIV-infected cells, with implications for HIV cure strategies.

Indexed as

HIV-1HIV InfectionsB-LymphocytesCD8-Positive T-LymphocytesHumansReceptors, CXCR5CXCR5 protein, humanReceptors, CXCR5

Identifiers

PMID34991160
PMCPMC8941472
OpenAlexW4205179193

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.