CD38 expression by neonatal human naïve CD4⁺T cells shapes their distinct metabolic state and high regulatory T cell potential

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 2, 2025

Abstract Neonatal life is marked by rapid antigen exposure, necessitating establishment of peripheral immune tolerance via conversion naïve CD4 + T cells into regulatory (Tregs). Here, we demonstrate that increased Treg differentiation naive from human cord blood versus adult integrally linked to their unique metabolic profile and elevated expression the NADase, CD38. Early a preference for glycolysis, which directly facilitates generation. We reveal an age-dependent gradient in CD38 levels on show high contributes both glycolytic state potential neonatal cells, effects are mediated at least part NAD-dependent deacetylase SIRT1. Thus, early window humans critically enabled immunometabolic compartment.

Language: Английский

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PD-1 prelimits both the cytotoxic and exhaustion potential in thymic CD8+ T cells and impacts the maintenance of peripheral tumor immunity

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 18, 2025

Abstract Durable T cell immunity against cancer depends on the continual replenishment of effector CD8+ cells. Thymic output has been correlated with favorable prognosis in patients across a range ages, suggesting that thymus is an important source for replenishing cells capable controlling progression. However, potential thymic mature and their regulation have not clearly defined. In this study, we identified ability single positive to gain after selection, but they are subject PD-1. We found previously undisclosed role PD-1 limiting both cytotoxic exhaustion peripheral Our results show although inhibition facilitates expansion cells, gradually lose antitumor activity within tumor tissues due advanced absence Thus, preset allows them rapidly respond malignant periphery, PD-1, as checkpoint, embedded selection balance function from exaggeration exhaustion. Therefore, propose strategy upholding capacity avoiding during early stages therapy needed achieve durable immunity.

Language: Английский

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Systematic review and quantitative meta-analysis of age-dependent human T-lymphocyte homeostasis

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 27, 2025

Objective To evaluate and quantitatively describe age-dependent homeostasis for a broad range of total T-cells specific T-lymphocyte subpopulations in healthy human subjects. Methods A systematic literature review was performed to identify collect relevant quantitative information on counts blood various organs. Both individual subject grouped (aggregated) data observations absolute relative values were digitized curated; cell phenotypes, gating strategies flow cytometry analyses, organs from which obtained, subjects’ number age also systematically inventoried. Age-dependent each subpopulation evaluated via weighted average calculation within pre-specified intervals, using piece-wise equal-effect meta-analysis methodology. Results In total, 124 studies comprising 11722 unique subjects encompassing 20 different – CD45+ CD3+ lymphocytes, as well CD4+ CD8+ naïve, recent thymic emigrants, activated, effector memory T-lymphocytes (total-memory, central-memory, effector-memory, resident-memory) collected included the final database comprehensive analysis. Blood most demonstrate decline with age, pronounced decrease first 10 years life. Conversely, display tendency increase older groups, particularly after ~50 age. Notably, an numbers is observed neonates infants (0 1 year age) towards less differentiated subpopulations, while into more emerges later (1 5 age). Conclusion humans performed, immune T-cell profiles function characterize generalized estimates across groups. Our study introduces description fundamental parameters characterizing maintenance evolution subsets based integration available organ-specific systems-level datasets. Overall, it provides up-to-date view physiological dynamics its variance may be used consistent reference gaining further mechanistic understanding status health disease.

Language: Английский

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Transcriptional control of T cell tissue adaptation and effector function in infants and adults

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 6, 2025

ABSTRACT The first years of life are essential for the development memory T cells, which rapidly populate body’s diverse tissue sites during infancy. However, degree to cell responses in early reflect those adulthood is unclear. Here, we use single RNA-sequencing resting and ex vivo activated cells from lymphoid mucosal tissues infant (aged 2-9 months) adult 40-65 years) human organ donors dissect transcriptional programming over age. Infant demonstrate a unique stem-like profile adaptation program, yet exhibit reduced activation capacity effector function relative adults. Using CRISPR-Cas9 knockdown, define Helios ( IKZF2 ) as critical regulator infant-specific program restricted state. Our findings reveal key mechanisms that control fate life.

Language: Английский

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Measuring thymic output across the human lifespan: a critical challenge in laboratory medicine

GeroScience, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 13, 2025

Abstract Age-associated thymic involution leads to a significant decline in T cell output, major contributor immunosenescence the elderly. Accurately measuring output is therefore critical for understanding mechanisms behind immune aging. Furthermore, robust quantification of essential various other clinical and research settings, including diagnosis immunodeficiencies monitoring reconstitution following therapeutic interventions like hematopoietic stem transplantation. Current methodologies include receptor excision circle (TREC) via quantitative polymerase chain reaction enumeration recent emigrants (RTEs) using flow cytometry. However, TREC-based assays are inherently insensitive subtle changes limiting their applicability beyond neonatal immunodeficiency screening. Similarly, RTE presents challenges; while surface markers exist CD4⁺ RTEs, validated CD8⁺ cytotoxic lymphocytes lacking. This represents knowledge gap, particularly as aging has been shown disproportionally affect CD8 pool. Moreover, cytometry effectively measures mature naïve cells, these cells do not accurately represent real-time they can persist peripheral circulation extended periods. These limitations highlight pressing need more accurate sensitive methods assess output. Improved measurement techniques would only enhance our context but also enable large-scale investigations into function driving its both health disease. In this review, we examine current humans, critically evaluate limitations, discuss emerging approaches address gaps field.

Language: Английский

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Lymph nodes link sex-biased immune aging to compromised antigen recognition

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 15, 2025

A diverse naive CD8 T cell repertoire is essential to provide broad protection against infection and cancer. Aging diminishes cells, reducing potential diversity leading lymph node contraction. Here, we revealed that this decline occurs earlier in males, resulting significant sex differences immunity during middle age. Earlier life, cells males become virtual memory prone premature senescence. Due androgen-driven thymic atrophy naïve are insufficiently replenished. Therapeutic thymus rejuvenation via testosterone ablation restored nodes of middle-aged male mice, enhanced tumor recognition. These findings show the crucial role age on repertoires suggest strategies restore immune function aging.

Language: Английский

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Tolerance After Hematopoietic Stem Cell Transplantation

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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Restraining the killers: regulation of T cell quiescence

Trends in Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

Language: Английский

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Unveiling the role of NAD glycohydrolase CD38 in aging and age-related diseases: insights from bibliometric analysis and comprehensive review

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: June 2, 2025

Background CD38, a glycoprotein with single transmembrane structure, is extensively found in erythrocytes, immune cells, and endothelial cells. Primarily located on cell membranes, it plays critical role metabolizing nicotinamide adenine dinucleotide (NAD), thereby maintaining NAD homeostasis vivo . As vital coenzyme, involved numerous biological processes, including energy metabolism, apoptosis, DNA repair. as major NAD-depleting enzyme, pivotal regulating intracellular levels various physiological processes. Given its significance, understanding the function of CD38 implications aging age-related diseases crucial for elucidating disease pathogenesis developing therapeutic strategies. Methods This study conducted bibliometric analysis to explore recent research trends advancements field CD38. Research articles were retrieved from Web Science database, followed by assessment using CiteSpace VOSviewer visualize key publication trends, contributions countries institutions, keyword distributions. Based analysis, insights synthesized elucidate diseases, underlying mechanisms, applications clinical evaluation, detection methods, interventions, targets. Results The revealed an exponential increase number published over time, United States China emerging leading hubs. predominant keywords included ‘CD38’ ‘blood-related disorders’. Furthermore, findings highlighted emphasizing mechanisms metabolism potential target. Moreover, current evaluation methods discussed, showcasing growing importance biomedical research. Conclusion underscores interest research, particularly diseases. highlight significance growth publications dominance this reflect global Future studies should further mechanistic advance strategies

Language: Английский

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Differential associations of anti-cytomegalovirus antibodies and soluble CD14 levels with immunosenescence in people living with HIV on long term antiretroviral therapy

Immunity & Ageing, Journal Year: 2024, Volume and Issue: 21(1)

Published: Dec. 21, 2024

Language: Английский

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