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Immune cells and brain parenchyma cells contribute to the pathogenesis of CM. However, a systematic examination of the changes that occur in the brain parenchyma region during CM at the single\u2010cell resolution is still poorly studied.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>\n                      To explore cell composition and CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cell infiltration, single\u2010cell RNA sequencing (scRNA\u2010seq) was performed on the brainstems of healthy and experimental cerebral malaria (ECM) mice. Then CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cell infiltration was confirmed by flow cytometry and immunofluorescence assays. Subsequently, the characteristics of the brain\u2010infiltrated CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells were analyzed. Finally, the interactions between parenchyma cells and brain\u2010infiltrated CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells were studied with an astrocytes\u2010CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cell cocultured model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The brainstem is the most severely damaged site during ECM. ScRNA\u2010seq revealed a large number of CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells infiltrating into the brainstem in ECM mice. Brain\u2010infiltrated CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells were highly activated according to scRNA\u2010seq, immunofluorescence, and flow cytometry assays. Further analysis found a subset of ki\u201067\n                      <jats:sup>+<\/jats:sup>\n                      CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells that have a higher transcriptional level of genes related to T cell function, activation, and proliferation, suggesting that they were exposed to specific antigens presented by brain parenchyma cells. Brain\u2010infiltrated CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells were the only prominent source of IFN\u2010\u03b3 in this single\u2010cell analysis. Astrocytes, which have a high interferon response, act as cross\u2010presenting cells to recruit and re\u2010activate brain\u2010infiltrated CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells. We also found that brain\u2010infiltrated CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells were highly expressed immune checkpoint molecule PD\u20101, while parenchyma cells showed up\u2010regulation of PD\u2010L1 after infection.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      These findings reveal a novel interaction between brain\u2010infiltrated CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells and parenchyma cells in the ECM brainstem, suggesting that the PD\u20101\/PD\u2010L1 signal pathway is a promising adjunctive therapeutic strategy for ECM targeting over\u2010activated CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cns.14431","type":"journal-article","created":{"date-parts":[[2023,9,12]],"date-time":"2023-09-12T04:14:40Z","timestamp":1694492080000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["CD8\n                    <sup>+<\/sup>\n                    T cell infiltration and proliferation in the brainstem during experimental cerebral malaria"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0880-4663","authenticated-orcid":false,"given":"Jun","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology and Parasitology Fourth Military Medical University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinghao","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Parasitology Fourth Military Medical University  Xi'an 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