{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T16:21:08Z","timestamp":1790266868241,"version":"4.1.0"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,8,13]],"date-time":"2021-08-13T00:00:00Z","timestamp":1628812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Inflammation after acute CNS injury plays a dual role. The interplay between immune cells and inflammatory mediators is critical to the outcome of injured neurons. Microglia\/macrophages are the first sensors and regulators of the immune response. We previously found that the enhancement of macrophages on neuron survival does not persist in thymectomized rats. How T lymphocytes and macrophages interact and benefit neuron survival is not fully elucidated. To this point, we introduce and characterize a cell-retina co-culture model that mimics the recruitment of peripheral lymphocytes at the injury site. Three-day post-optic nerve transection (ONT) in Fischer 344 rats, transected retinas were co-cultured with either peripheral lymph node-derived lymphocytes (injury-activated) or from intact rats as the control. The injury-activated lymphocytes preserved retinal ganglion cells (RGCs) and caused extensive retina microglial\/macrophage infiltration. CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup> T cells were upregulated in the injury-activated lymphocytes and increased RGC survival, suggesting that CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup> T cells suppressed the cytotoxicity of control lymphocytes. When microglia\/macrophages were depleted by clodronate, neuron loss was more extensive, the cytotoxicity of control lymphocytes on RGCs was alleviated, and the neuroprotective effect of injury-activated lymphocytes remain unchanged Cytokine detection showed an increase in IL-6 and TNF-\u03b1 levels that were reduced with microglia\/macrophage depletion. Our results suggest that microglial\/macrophage infiltration into axotomized retinas promotes RGC survival by secreting cytokines to induce CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup> T cells and suppress T cell-mediated RGC toxicity. These findings reveal a specific role for microglia\/macrophage and CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup> T cells in inflammation after CNS injury, thereby adding to the mechanistic basis for the development of microglial\/macrophage modulation therapy for traumatic CNS injury.<\/jats:p>","DOI":"10.3389\/fimmu.2021.687898","type":"journal-article","created":{"date-parts":[[2021,8,13]],"date-time":"2021-08-13T14:02:55Z","timestamp":1628863375000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Microglia\/Macrophages and CD4+CD25+ T Cells Enhance the Ability of Injury-Activated Lymphocytes to Reduce Traumatic Optic Neuropathy In 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