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PD1 and CD73 on naïve CD4+ T cells synergistically limit responses to self

GSE263393 Mus musculus Expression profiling by high throughput sequencing 9 samples Submitted 2024/09/16 Platform GPL24247
Summary
Vaccination with self and foreign peptides induces weak and strong expansion of antigen-specific CD4 T cells, respectively, but the mechanism is not known. We tested how much the naïve CD4 T cell repertoires specific for self antigens are shaped by negative selection in the thymus by computational analysis of the entire mouse MHCII peptidome and found that negative selection only partially explains the difference between responses to self and foreign. In naïve (uninfected, unimmunized) mice, RNA-Seq identified higher PD1 and CD73 expression on self-specific compared to foreign-specific CD4 T cells. Pharmacological or genetic blockade of PD1 and CD73 significantly increased the vaccine-induced expansion of self-specific CD4 T cells and moved their transcriptomes toward those of foreign-specific CD4 T cells. We conclude that PD1 and CD73 synergistically limit CD4 T cell responses to self. This discovery has implications for the development of tolerogenic vaccines and cancer immunotherapy.
Published in
PD-1 and CD73 on naive CD4(+) T cells synergistically limit responses to self
Nettersheim FS, Brunel S, Sinkovits RS et al. · Nature immunology 2025 · PMID 39572641 · doi:10.1038/s41590-024-02021-6
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Also filed as BioProject PRJNA1097455 and SRA study SRP500406. Searching any of these in the dataset finder brings you back here.

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