Abstract
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.
Highlights
Pneumocystis pneumonia (PCP) is a life-threatening complication in human immunodeficiency virus (HIV)-negative immunocompromised patients with more abrupt clinical manifestation, worse prognosis, and higher mortality than HIV patients (Roblot et al, 2002; Roux et al, 2014)
To investigate the dynamics and diversity of the T cell repertoire during PCP, we first performed scRNA-seq and scTCR-seq on lung CD45+ cells from mice infected with Pneumocystis for 0–4 weeks (Figure 1A)
To simultaneously analyze the transcriptome and immune repertoire of T cells, we only retained the barcodes detected in both scRNA-seq and scTCRseq
Summary
Pneumocystis pneumonia (PCP) is a life-threatening complication in human immunodeficiency virus (HIV)-negative immunocompromised patients with more abrupt clinical manifestation, worse prognosis, and higher mortality than HIV patients (Roblot et al, 2002; Roux et al, 2014). T Cell Repertoire in PCP studies attempted to elucidate the specific function of CD4+ T cells subsets and found that diverse CD4+ T cells subsets participate in the immune response against Pneumocystis such as Th1 (Garvy et al, 1997), Th17 (Rudner et al, 2007), Treg (McKinley et al, 2006), and Th9 cells (Li et al, 2018). Those studies were based on whole tissues or bulk populations of cells, which could not account for T-cell heterogeneity at a high resolution, and may obscure some important mechanistic mediators
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