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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.

Single-Cell TCR Sequencing Reveals the Dynamics of T Cell Repertoire Profiling During Pneumocystis Infection