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Single-cell TCR sequencing reveals the dynamics of T cell repertoire profiling during Pneumocystis infection

ABSTRACT: Single-cell TCR sequencing reveals the dynamics of T cell repertoire profiling during Pneumocystis infection

PROVIDER: PRJNA659231 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12514624_1.fastq.gz	Fastqsanger.gz
	SRR12514624_2.fastq.gz	Fastqsanger.gz
	SRR12514625_1.fastq.gz	Fastqsanger.gz
	SRR12514625_2.fastq.gz	Fastqsanger.gz
	SRR12514626_1.fastq.gz	Fastqsanger.gz

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Single-cell TCR sequencing reveals the dynamics of T cell repertoire profiling during Pneumocystis infection

Project description:T cell response exert critical roles in the host adaptive immunity against Pneumocystis. However, the dynamics and diversity of T cell immune repertoire in HIV-negative Pneumocystis remains unknown. In this study, single-cell RNA and T cell receptor (TCR) sequencing were applied on cells sorted from lung tissues of mice infected with Pneumocystis from 0 to 4 weeks. Our data demonstrated clonally CD4+ T cells and CD8+ T cells expanded in response to Pneumocystis, which marked by highly expressed genes associated with T cell activation and cytotoxicity. The length distribution of CDR3 AA and gene usage variability were similar between Pneumocystis infected mice and control group. We tracked the transcriptome and TCR immune repertoires profiles of expanded lymphocyte clones during Pneumocystis infection, which demonstrate a reconstitution of the TCR immune repertoire after Pneumocystis infection.

2021-03-26 | GSE156843 | GEO

Signatures of B cell receptor repertoire following Pneumocystis infection

Project description:B cells play vital roles in host defense against Pneumocystis infection, however, the features of B cell receptor (BCR) repertoire in the disease progression remain unclear. Here we integrated single-cell RNA sequencing and single-cell BCR sequencing of immune cells from mice lung at uninfected state and 1-4 weeks postinfection, in order to illustrate the dynamic nature of B cell responses during Pneumocystis infection. We identified continuously increased plasma cells and an elevated ratio of (IgA+ IgG) to (IgD+ IgM) after infection. Moreover, Pneumocystis infection was associated with an increase of a naïve B subset characterized by elevated expression of the transcription factor ATF3. The proportion of clonal expanded cells progressively increased, with the BCR diversity decreased. Biased usage of V(D)J genes was observed, and the usage frequency of IGHV9-3 was elevated. Overall, these results present a detailed atlas of B cell transcriptional changes and BCR repertoire features in the context of Pneumocystis infection.

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Signatures of B cell receptor repertoire following Pneumocystis infection

Project description:Signatures of B cell receptor repertoire following Pneumocystis infection

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TCR repertoire analysis revealed the highly conserved TCR repertoire in the bilateral tumor in mice

Project description:Temporal analysis of T-cell receptor (TCR) repertoire has been used to monitor treatment-induced changes in antigen-specific T cells in patients with cancer. However, lack of experimental model that allows the temporal analysis of TCR repertoire in same individual in homogeneous population limit the understanding of causal relationship between changes in TCR repertoire and antitumor responses. A bilateral tumor model, in which tumor cells were inoculated into the bilateral backs of mice, can be used for temporal analysis in TCR repertoire. In this study, we examined the prerequisite for this strategy: TCR repertoire are conserved between the bilateral tumor with same growth rate. The bilateral tumors with equivalent tumor size and draining lymph nodes (dLN) were collected 13 days after the tumor inoculation to analyze the TCR repertoire of CD4+ and CD8+ T cells. Most of the tumor-infiltrating T-cell clones were highly conserved between the bilateral tumors, and the extent of clonal expansion was equivalent. In addition, the similarity between bilateral tumors were equivalent to the heterogeneity in one side of the tumor. The similarity of TCR repertoire in the bilateral dLN was markedly lower than that of the tumor, suggesting that tumor-reactive T-cell clones induced independently in each dLN were integrated during recirculation and then infiltrated the tumor. These findings suggest that our bilateral tumor model is suitable for temporal monitoring of TCR repertoire to evaluate temporal and treatment-induced changes in tumor-reactive T-cell clones.

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Malt1PD TCR repertoire

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TCR repertoire analysis revealed the highly conserved TCR repertoire in the bilateral tumor in mice

Project description:TCR repertoire analysis revealed the highly conserved TCR repertoire in the bilateral tumor in mice

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Single-Cell TCR Sequencing Reveals the Dynamics of T Cell Repertoire Profiling During <i>Pneumocystis</i> Infection.

Project description:T cell responses play critical roles in host adaptive immunity against Pneumocystis. However, the dynamics and diversity of the T cell immune repertoire in human immunodeficiency virus (HIV)-negative Pneumocystis pneumonia (PCP) remains unclear. In this study, single-cell RNA and single-cell T cell receptor (TCR) sequencing were applied to cells sorted from lung tissues of mice infected with Pneumocystis. Our findings demonstrated the clonal cells were mainly composed of CD4+ T cells in response to Pneumocystis, which were marked by highly expressed genes associated with T cell activation. Mice infected with Pneumocystis showed reduced TCR diversity in CD4+ T cells and increased diversity in CD8+ T cells compared with uninfected controls. Furthermore, Th17 cells were mostly clonal CD4+ T cells, which exhibited the phenotype of tissue-resident memory-like Th17 cells. In addition, Pneumocystis-infected mice showed biased usage of TCRβ VDJ genes. Taken together, we characterized the transcriptome and TCR immune repertoires profiles of expanded T cell clones, which demonstrate a skewed TCR repertoire after Pneumocystis infection.

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