Browse
Submit Data
Databases
API
Help

Dataset Information

25 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

CD5 levels define functionally heterogeneous populations of naive human CD4⁺ T cells.

ABSTRACT: Studies in murine models show that subthreshold TCR interactions with self-peptide are required for thymic development and peripheral survival of naïve T cells. Recently, differences in the strength of tonic TCR interactions with self-peptide, as read-out by cell surface levels of CD5, were associated with distinct effector potentials among sorted populations of T cells in mice. However, whether CD5 can also be used to parse functional heterogeneity among human T cells is less clear. Our study demonstrates that CD5 levels correlate with TCR signal strength in human naïve CD4⁺ T cells. Further, we describe a relationship between CD5 levels on naïve human CD4⁺ T cells and binding affinity to foreign peptide, in addition to a predominance of CD5^hi T cells in the memory compartment. Differences in gene expression and biases in cytokine production potential between CD5^lo and CD5^hi naïve human CD4⁺ T cells are consistent with observations in mice. Together, these data validate the use of CD5 surface levels as a marker of heterogeneity among human naïve CD4⁺ T cells with important implications for the identification of functionally biased T- cell populations that can be exploited to improve the efficacy of adoptive cell therapies.

SUBMITTER: Sood A

PROVIDER: S-EPMC8251777 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

CD5 levels define functionally heterogeneous populations of naïve human CD4+ T cells

Project description:Studies from mouse models show that differences in self-reactivity, as read-out by CD5 levels, identifies naïve T cell subsets with distinct functional properties during an immune response. Whether CD5 levels can also be used to parse functional biases in naive human CD4+ T cells is incompletely understood. Our study establishes CD5 as a reliable marker of T cell self-reactivity and functional heterogeneity in human CD4+ T cells.

2020-04-15 | GSE148662 | GEO

CD5 levels define functionally heterogeneous populations of naïve human CD4+ T cells

Project description:CD5 levels define functionally heterogeneous populations of naïve human CD4+ T cells

| PRJNA625305 | ENA

Human CD5+ Innate Lymphoid Cells Are Functionally Immature and Their Development from CD34+ Progenitor Cells Is Regulated by Id2.

Project description:Innate lymphoid cells (ILCs) have emerged as a key cell type involved in surveillance and maintenance of mucosal tissues. Mouse ILCs rely on the transcriptional regulator Inhibitor of DNA-binding protein 2 (Id2) for their development. Here, we show that Id2 also drives development of human ILC because forced expression of Id2 in human thymic progenitors blocked T cell commitment, upregulated CD161 and promyelocytic leukemia zinc finger (PLZF), and maintained CD127 expression, markers that are characteristic for human ILCs. Surprisingly CD5 was also expressed on these in vitro generated ILCs. This was not an in vitro artifact because CD5 was also found on ex vivo isolated ILCs from thymus and from umbilical cord blood. CD5 was also expressed on small proportions of ILC2 and ILC3. CD5+ ILCs were functionally immature, but could further differentiate into mature CD5- cytokine-secreting ILCs. Our data show that Id2 governs human ILC development from thymic progenitor cells toward immature CD5+ ILCs.

| S-EPMC5583608 | biostudies-literature

Memory CD4 T cell subsets are kinetically heterogeneous and replenished from naive T cells at high levels.

Project description:Characterising the longevity of immunological memory requires establishing the rules underlying the renewal and death of peripheral T cells. However, we lack knowledge of the population structure and how self-renewal and de novo influx contribute to the maintenance of memory compartments. Here, we characterise the kinetics and structure of murine CD4 T cell memory subsets by measuring the rates of influx of new cells and using detailed timecourses of DNA labelling that also distinguish the behaviour of recently divided and quiescent cells. We find that both effector and central memory CD4 T cells comprise subpopulations with highly divergent rates of turnover, and show that inflows of new cells sourced from the naive pool strongly impact estimates of memory cell lifetimes and division rates. We also demonstrate that the maintenance of CD4 T cell memory subsets in healthy mice is unexpectedly and strikingly reliant on this replenishment.

| S-EPMC5426903 | biostudies-literature

Specific transcriptional programs differentiate ICOS from CD28 costimulatory signaling in human Naive CD4+ T cells.

Project description:Costimulatory molecules of the CD28 family play a crucial role in the activation of immune responses in T lymphocytes, complementing and modulating signals originating from the T-cell receptor (TCR) complex. Although distinct functional roles have been demonstrated for each family member, the specific signaling pathways differentiating ICOS- from CD28-mediated costimulation during early T-cell activation are poorly characterized. In the present study, we have performed RNA-Seq-based global transcriptome profiling of anti-CD3-treated naïve CD4+ T cells upon costimulation through either inducible costimulator (ICOS) or CD28, revealing a set of signaling pathways specifically associated with each signal. In particular, we show that CD3/ICOS costimulation plays a major role in pathways related to STAT3 function and osteoarthritis (OA), whereas the CD3/CD28 axis mainly regulates p38 MAPK signaling. Furthermore, we report the activation of distinct immunometabolic pathways, with CD3/ICOS costimulation preferentially targeting glycosaminoglycans (GAGs) and CD3/CD28 regulating mitochondrial respiratory chain and cholesterol biosynthesis. These data suggest that ICOS and CD28 costimulatory signals play distinct roles during the activation of naïve T cells by modulating distinct sets of immunological and immunometabolic genes.

| S-EPMC9484324 | biostudies-literature

CD28 and CD57 define four populations with distinct phenotypic properties within human CD8+ T cells.

Project description:After repeated antigen exposure, both memory and terminally differentiated cells can be generated within CD8+ T cells. Although, during their differentiation, activated CD8+ T cells may first lose CD28, and CD28- cells may eventually express CD57 as a subsequent step, a population of CD28+ CD57+ (DP) CD8+ T cells can be identified in the peripheral blood. How this population is distinct from CD28- CD57- (DN) CD8+ T cells, and from the better characterized non-activated/early-activated CD28+ CD57- and senescent-like CD28- CD57+ CD8+ T cell subsets is currently unknown. Here, RNA expression of the four CD8+ T cell subsets isolated from human PBMCs was analyzed using microarrays. DN cells were more similar to "early" highly differentiated cells, with decreased TNF and IFN-? production, impaired DNA damage response and apoptosis. Conversely, increased apoptosis and expression of cytokines, co-inhibitory, and chemokine receptors were found in DP cells. Higher levels of DP CD8+ T cells were observed 7 days after Hepatitis B vaccination, and decreased levels of DP cells were found in rheumatoid arthritis patients. More DP and DN CD8+ T cells were present in the bone marrow, in comparison with PBMCs. In summary, our results indicate that DP and DN cells are distinct CD8+ T cell subsets displaying defined properties.

| S-EPMC7079235 | biostudies-literature

Predominant VH1-69 IgBCR Clones Show Higher Expression of CD5 in Heterogeneous Chronic Lymphocytic Leukemia Populations.

Project description:The immunoglobulin B cell receptor (IgBCR) expressed by chronic lymphocytic leukemia (CLL) B cells plays a pivotal role in tumorigenesis, supporting neoplastic transformation, survival, and expansion of tumor clones. We demonstrated that in the same patient, two or more CLL clones could coexist, recognized by the expression of different variable regions of the heavy chain of IgBCR, composing the antigen-binding site. In this regard, phage display screening could be considered the easier and most advantageous methodology for the identification of small peptide molecules able to mimic the natural antigen of the tumor IgBCRs. These molecules, properly functionalized, could be used as a probe to specifically identify and isolate single CLL subpopulations, for a deeper analysis in terms of drug resistance, phenotype, and gene expression. Furthermore, CLL cells express another surface membrane receptor, the CD5, which is commonly expressed by normal T cells. Piece of evidence supports a possible contribution of CD5 to the selection and maintenance of autoreactivity in B cells and the constitutive expression of CD5 on CLL cells could induce pro-survival stimuli. In this brief research report, we describe a peptide-based single-cell sorting using as bait the IgBCR of tumor cells; in the next step, we performed a quantitative analysis of CD5 expression by qRT-PCR related to the expressed IgBCR. Our approach could open a new perspective for the identification, isolation, and investigation of all subsets of IgBCR-related CLL clones, with particular attention to the more aggressive clones.

| S-EPMC8249760 | biostudies-literature

TGF-β inhibits IL-7-induced proliferation in memory but not naive human CD4+ T cells.

Project description:TGF-β is a potent suppressor of T cell activation and expansion. Although the antiproliferative effects of TGF-β are well characterized in TCR-activated cells, the effects of TGF-β on T cell proliferation driven by homeostatic cytokines, such as IL-7, are poorly defined. In the current study, we found that TGF-β inhibits IL-7-induced proliferation in memory, but not in naive human CD4+ T cells. TGF-β impaired c-myc induction in all CD4+ T cell maturation subsets, although the impairment was less sustained in naive CD4+ T cells. TGF-β had no discernible effect on IL-7R signaling (p-STAT-5, p-Akt, or p-S6) in memory T cells but selectively enhanced p-S6 signaling in naive T cells. The inhibitory effects of TGF-β on memory T cell proliferation were partially overcome by chemical inhibition of GSK-3, which also led to enhanced c-myc expression. These data suggest that TGF-β could play an important role in limiting homeostatic proliferation of memory T cells. Our observations also point toward a novel strategy to subvert TGF-β-mediated inhibition of memory T cells by targeting GSK-3 for inhibition.

| S-EPMC6608080 | biostudies-literature

Naive and memory CD4+ T cell subsets can contribute to the generation of human Tfh cells.

Project description:CD4+ T follicular helper cells (Tfh) promote B cell maturation and antibody production in secondary lymphoid organs. By using an innovative culture system based on splenocyte stimulation, we studied the dynamics of naive and memory CD4+ T cells during the generation of a Tfh cell response. We found that both naive and memory CD4+ T cells can acquire phenotypic and functional features of Tfh cells. Moreover, we show here that the transition of memory as well as naive CD4+ T cells into the Tfh cell profile is supported by the expression of pro-Tfh genes, including transcription factors known to orchestrate Tfh cell development. Using this culture system, we provide pieces of evidence that HIV infection differentially alters these newly identified pathways of Tfh cell generation. Such diversity in pathways of Tfh cell generation offers a new framework for the understanding of Tfh cell responses in physiological and pathological contexts.

| S-EPMC8693005 | biostudies-literature

Comparative Analysis of Global Proteome and Lysine Acetylome Between Naive CD4+ T Cells and CD4+ T Follicular Helper Cells.

Project description:As a subgroup of CD4+ T helper cells, follicular helper T (Tfh) cells provide help to germinal center B cells and mediate the development of long-lived humoral immunity. Dysregulation of Tfh cells is associated with several major autoimmune diseases. Although recent studies showed that Tfh cell differentiation is controlled by the transcription factor Bcl6, cytokines, and cell-cell signals, limited information is available on the proteome and post-translational modifications (PTMs) of proteins in human Tfh cells. In the present study, we investigated quantitative proteome and acetylome in human naive CD4+ T cells and in vitro induced Tfh (iTfh) cells using the tandem mass tag (TMT) labeling technique, antibody-based affinity enrichment, and high-resolution liquid chromatography-mass spectrometry (LC-MS)/mass spectrometry (MS) analysis. In total, we identified 802 upregulated proteins and 598 downregulated proteins at the threshold of 1.5-fold in iTfh cells compared to naive CD4+ T cells. With the aid of intensive bioinformatics, the biological process, the cellular compartment, the molecular function, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and protein-protein interaction of these differentially expressed proteins were revealed. Moreover, the acetylome data showed that 22 lysine (K) acetylated proteins are upregulated and 26 K acetylated proteins are downregulated in iTfh cells compared to the naive CD4+ T cells, among which 11 differentially acetylated K residues in core histones were identified, indicating that protein acetylation and epigenetic mechanism are involved in regulating Tfh cell differentiation. The study provides some important clues for investigating T cell activation and Tfh cell differentiation.

| S-EPMC8027069 | biostudies-literature