Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Cytolytic CD8+ T cells infiltrate germinal centers to limit ongoing HIV replication in spontaneous controller lymph nodes

ABSTRACT: Follicular CD8+ T cells (fCD8) mediate surveillance in lymph node (LN) germinal centers against lymphotropic infections and cancers, but precise mechanisms by which these cells mediate immune control remain incompletely resolved. To address this, we investigated functionality, clonotypic compartmentalization, spatial localization, phenotypic characteristics, and transcriptional profiles of LN-resident virus-specific CD8+ T cells in persons who control HIV without medications. Antigen-induced proliferative and cytolytic potential consistently distinguished spontaneous controllers from noncontrollers. T cell receptor analysis revealed complete clonotypic overlap between peripheral and LN-resident HIV-specific CD8+ T cells. Transcriptional analysis of LN CD8+ T cells revealed gene signatures of inflammatory chemotaxis and antigen-induced effector function. In HIV controllers, the cytotoxic effectors perforin and granzyme B were elevated among virus-specific CXCR5+ fCD8s proximate to foci of HIV RNA within germinal centers. These results provide evidence consistent with cytolytic control of lymphotropic infection supported by inflammatory recruitment, antigen-specific proliferation, and cytotoxicity of fCD8s.

ORGANISM(S): Homo sapiens

PROVIDER: GSE196549 | GEO | 2023/04/20

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

HIV specific CD8+ Trm-like cells in tonsils express exhaustive signatures in the absence of natural HIV control [Seqwell]

Project description:Lymphoid tissues are an important HIV reservoir site that persists in the face of antiretroviral therapy and natural immunity. Targeting these reservoirs by harnessing the antiviral activity of local tissue-resident memory (TRM) CD8+ T-cells is of great interest, but limited data exist on TRM-like cells within lymph nodes of people living with HIV (PLWH). Here, we studied tonsil CD8+ T-cells obtained from PLWH and uninfected controls from South Africa. We show that these cells are preferentially located outside the germinal centers (GCs), the main reservoir site for HIV, and display a low cytolytic and transcriptionally TRMlike profile distinct from blood CD8+ T-cells. In PLWH, CD8+ TRM-like cells are highly expanded and adopt a more cytolytic, activated, and exhausted phenotype not reversed by antiretroviral therapy (ART). This phenotype was enhanced in HIV-specific CD8+ T-cells from tonsils compared to matched blood suggesting a higher antigen burden in tonsils. Single-cell transcriptional and clonotype resolution showed that these HIV-specific CD8+ T-cells in the tonsils express heterogeneous signatures of T-cell activation, clonal expansion, and exhaustion ex-vivo. Interestingly, this signature was absent in a natural HIV controller, who expressed lower PD-1 and CXCR5 levels and reduced transcriptional evidence of T-cell activation, exhaustion, and cytolytic activity. These data provide important insights into lymphoid tissue-derived HIVspecific CD8+ TRM-like phenotypes in settings of HIV remission and highlight their potential for immunotherapy and targeting of the HIV reservoirs.

2022-10-12 | GSE215125 | GEO

HIV specific CD8+ Trm-like cells in tonsils express exhaustive signatures in the absence of natural HIV control [smart-seq 2]

2022-10-12 | GSE215126 | GEO

Cytolytic CD8+ T cells infiltrate germinal centers to limit ongoing HIV replication in spontaneous controller lymph nodes

Project description:Cytolytic CD8+ T cells infiltrate germinal centers to limit ongoing HIV replication in spontaneous controller lymph nodes

| PRJNA805304 | ENA

MicroRNA Profile in CD8+ T-lymphocytes from HIV-Infected Individuals: Relationship with Disease Progression

Project description:The relationship between host microRNAs (miRNA), viral control and immune response has not been elucidated in the field of HIV yet. The aim of this study was to assess the differential miRNA profile in CD8+ T-cells between HIV-infected individuals who differ in terms of disease progression. A total of 136 RNAs (miRNAs) were analyzed: 68 RNAs from resting CD8+ T-cells and the respective 68 RNAs from stimulated CD8+ T-cells from Elite Controllers (EC, n=15), Viremic Controllers (VC, n=15), Viremic Progressors (VP, n=13), Treated Patients (ART, n=14) and Uninfect Donors (HIV-, n=11).

2015-08-04 | E-GEOD-71650 | biostudies-arrayexpress

Murine HIV-gagP24 CD8 T cells: bone marrow vs Lymph node

Project description:Transcriptional profiling to examine differences resulting from priming of virus-specific CD8 T cells in draining lymph node and in bone marrow, following intradermal injection of modified virus Ankara (MVA)-HIV gag. Transcriptional profiling of mouse pentamer H2kD-AMQMLKETI (HIV-gagP24) CD8 T cells from draining lymph nodes(LN) and bone marrow (BM ) 5 days following intradermal injection of MVA-HIV gag, and compared to naive (CD62L Hi CD44 int) CD8+ T cells from lymph node of naive mice (NTc). Three-condition experiment, BM, LN and NTc. Experimental replicates: 5 BM, 5 LN, 5 NTc, RNA pooled from 3 independant experiments of 5 mice each.

2012-10-23 | E-GEOD-41736 | biostudies-arrayexpress

Transcriptional profiling of CD4 T-cells in HIV-1 infected patients

2011-01-01 | GSE23879 | GEO

Transcriptional profiling of CD4 T-cells in HIV-1 infected patients

Project description:HIV-1 elite controllers maintain undetectable levels of viral replication in the absence of antiretroviral therapy, but their underlying immunological and virological characteristics may vary. Here, we used a whole-genome transcriptional profiling approach to characterize gene expression signatures of CD4 T cells from an unselected cohort of elite controllers. In the majority of elite controllers, transcriptional profiles were similar to HAART-treated patients, while being different from HIV-1 negative persons. Yet, a smaller proportion of elite controllers showed an opposite gene expression pattern that was indistinguishable from HIV-1 negative persons, but different from HAART-treated individuals. Elite controllers with this gene expression signature had significantly higher CD4 T cell counts, smaller levels of HIV-1-specific CD8+ T cell responses and tended to have lower residual HIV-1 viremia as determined by ultra-sensitive single-digit PCR, but did not differ from other elite controllers in terms of HLA class I alleles, age or sex. Thus, these data identify a specific subgroup of elite controllers whose clinical, immunological and gene expression characteristics approximate those of HIV-1 negative persons. PBMC from study persons were stained with monoclonal antibodies against CD3, CD4 and HLA-DR, and subsequently subjected to live sorting at 70 psi using an ARIA cell sorting device (Becton Dickinson) located in a specifically designated biosafety cabinet. Following mRNA extraction form the sorted cells (RNAeasy kit, Qiagen), whole genome transcriptional profiling was performed using WG-DASL microarrays (Illumina) according to standard protocols. We included an unselected cohort of elite controllers (n = 12) and two background populations of HIV-1 negative persons (n = 9) and HIV-1 infected persons effectively treated with HAART (n = 14). Four replicates were included in the study.

2011-01-01 | E-GEOD-23879 | biostudies-arrayexpress

Sorted Bulk and KK10-specific CD8+ T cells from HLA-B*2705 HIV elite controllers before and after KK10 peptide stimulation

Project description:CD8+ T cells from HLA-B*2705 HIV+ elite controllers Hi and Lo samples are CD8+ T cells bound by an HLA-B*2705 tetramer specific for the Gag p24 peptide KK10 PBMCs were incubated in the presence and absence of KK10 peptide for 6 days, and CD8+ and KK10-specific CD8+ T cell were sorted by flow cytometry

2014-04-23 | E-GEOD-56971 | biostudies-arrayexpress

Sorted Bulk and KK10-specific CD8+ T cells from HLA-B*2705 HIV elite controllers before and after KK10 peptide stimulation

Project description:CD8+ T cells from HLA-B*2705 HIV+ elite controllers Hi and Lo samples are CD8+ T cells bound by an HLA-B*2705 tetramer specific for the Gag p24 peptide KK10

2014-04-23 | GSE56971 | GEO

Distinct SIV-specific lymphoid tissue CD8 T cells exhibit simultaneous effector and stem-like profiles and associate with limited SIV persistence

Project description:HIV cure efforts are increasingly focused on harnessing CD8 T cell functions; however, a deeper understanding of CD8 T cells promoting HIV control is necessary to properly inform therapeutic approaches. Here, we identified a novel TOX-expressing CD8 T cell population associated with control of SIV infection in lymphoid tissue of rhesus macaques defined as an antigen-responsive TCF1+ CD39+ subset expressing high levels of TOX and inhibitory receptors but lower levels of canonical cytolytic molecules such as granzyme B, granzyme A, and perforin. Transcriptional analysis of SIV-specific CD8 T cells, as well as proteomic analysis of purified CD8 T cell subsets, revealed these TCF1+ CD39+ cells as an intermediate effector population retaining stem-like features while maintaining a lineage relationship with terminal effector cells. TCF1+ CD39+ CD8 T cells expressed higher levels of CXCR5 than terminally differentiated cells, were found at higher frequency in follicular micro-environments, and were preferentially located in the proximity of SIV-RNA+ cells both in lymph node T cell zone and B cell follicles. Importantly, their frequency was strongly associated with reduced plasma viremia and lower reservoir size. Finally, we confirmed the presence of a highly similar TOX-enriched TCF1+ CD39+ cell population in lymph node biopsies from ART-naïve and ART-treated people living with HIV. Collectively, these data identify a unique population of lymphoid CD8 T cells possessing both stem-like and effector properties that contribute to limiting HIV/SIV persistence.

2024-06-11 | PXD050498 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data