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Inflammation alters young and old CD8 T cells

ABSTRACT: Inflammation alters young and old CD8 T cells

PROVIDER: PRJNA904766 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR22396566.fastq.gz	Fastqsanger.gz
	SRR22396567.fastq.gz	Fastqsanger.gz
	SRR22396568.fastq.gz	Fastqsanger.gz
	SRR22396569.fastq.gz	Fastqsanger.gz
	SRR22396570.fastq.gz	Fastqsanger.gz

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Inflammation alters young and old CD8 T cells

Project description:Inflammation plays a significant role in lung infection caused by Mycobacterium tuberculosis (M.tb), and both adaptive and innate lymphocytes can affect infection control. How inflammation affects infection is understood in a broad sense, including inflammaging (chronic inflammation) seen in the elderly, but the explicit role that inflammation can play in regulation of lymphocyte function is not known. To fill this knowledge gap, we used an acute lipopolysaccharide (LPS) treatment in young mice and studied lymphocyte responses compared to old mice, focusing on CD8 T cell subsets. LPS treatment decreased the total numbers of T cells in the lungs of LPS mice, while also increasing the number of activated T cells. We demonstrate that lung CD8 T cells from LPS mice became capable of an antigen independent innate-like IFN-gamma secretion, dependent on IL-12p70 stimulation, paralleling innate-like IFN-gamma secretion of lung CD8 T cells from old mice. Overall, this study provides information on how acute inflammation can affect lymphocytes, particularly CD8 T cells, which could potentially affect immune control of various disease states.

2023-09-06 | GSE218660 | GEO

scRNA-seq analysis of mouse splenic CD8 T cells 1 month post transfer of CD8 T cells from 3 months old donor into 24 months old recipient

Project description:Aging is associated with systemic chronic inflammation (inflammaging) that leads to impaired physiological functions and vulnerability to several diseases. However, underlying alterations in aged immune system resulting in gradual loss of immune fitness remain unclear. Using a combination of CD8 T cell transfer from young to old and from old to young mice and single-cell RNA sequencing, we characterized the age-associated alterations in CD8 T cells. We transferred 2 millions of purified CD8+ T cells pooled from 3 CD45.1 C57BL/6J 3 months old female mice (donor) by i.v. injection into CD45.2 C57BL/6J 24 months old female mouse (recipient) and sorted CD45.1+CD3e+CD8a+ and CD45.2+CD3e+CD8a+ T cells from the spleen 1 month post transfer to perform scRNA/TCR-seq.

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Project description:Define,(a) intrinsic differences and (b) changes occuring upon TCR activation in genetic profiles of naive CD4+ and CD8+ T cells from young and old animals, to identify candidate genes altered in old T cells involved in impairement of immune response in order to restore immune function in the old. Activation dependant time series on sorted naive (CD62Lhi/CD44lo) CD4 and CD8 T cells from young and old animals-Each time point contains RNA pooled from 4 independent sortings

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Transcription profiling of CD8 T cell subsets from healthy young and elderly persons

Project description:We isolated highly purified CD8+CD28+ and CD8+CD28- T cell populations from healthy young and elderly persons for gene expression profiling using Affymetrix oligonucleotide microarrays. We demonstrate that the gene expression profile of CD8+CD28- T cells is very similar in young and elderly persons. In contrast, CD8+CD28+ in elderly differ from CD8+CD28+ in young persons. Hierarchical clustering revealed that CD8+CD28+ in elderly are located between CD8+CD28+ in young and CD8?CD28- (young and old) T cells regarding their differentiation state. Our study demonstrates a dichotomy of gene expression levels between CD8+CD28+ T cells in young and elderly persons but a similarity between CD8+CD28- T cells in young and elderly persons. As CD8+CD28+ T cells from elderly and young persons are distinct due to a different composition of the population, these results suggest that the gene expression profile does not depend on chronological age but depends on the differentiation state of the individual cell types.

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mRNA expression of young, mid-old, and old fibroblasts

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Project description:The reciprocal decline in naive (TN) and increase in virtual (TVM) and true memory (TTM) CD8 T-cell frequencies upon aging is incompletely understood. We established the glycosphingolipid asialo-GM1 (AsGM1) marker present on >70% of TVM/TTM and 5-15% TN to target their immune-regulatory and homeostatic potential. We identified a novel AsGM1+ old CD8 TN-subset that was related to antigen-experienced AsGM1+ CD8 TTM and showed an initial immune-regulatory (Pdcd1, Il10) gene expression signature. The program for AsGM1+ CD8 T-subsets was imprinted genetically in young and old hematopoietic stem cells that reconstitute young and old donor-type immune systems in lymphophenic RAG1-/- mice within 16 weeks, respectively. However, antibody-mediated depletion of AsGM1+ T cells in old mice revealed a disturbed recovery of CD8 TVM resulting in a rejuvenated T-subset composition and T-cell priming capacity upon DNA-vaccination. Old CD8 TVM and IL10+ PD-1+ TTM exerted immune-regulatory functions and suppressed CD3/CD28-mediated activation of TN in vitro. Glycosphingolipids thus are attractive to identify and target novel T-subsets.

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