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| Item Type: | Dataset |
|---|---|
| Title: | The AICL-KLRF1 axis supports CD4-CD8 T cell communication and cytokine competence in pre-exhausted CD8+ T cells |
| Creators Name: | Barone, Matthias, Peidli, Stefan, Neuschulz, Anika, Riesterer, Karla, Iwert, Christina, Junquera, Laia, Sai, Somesh, Bolaji, Olufemi, Bakoueva, Diana, Appelt, Christine, Obermayer, Benedikt, Klinger, Bertram, Trinks, Alexandra, Sieber, Anja, Blüthgen, Nils and Sawitzki, Birgit |
| Abstract: | Memory-like or precursor exhausted (Tpex) CD8⁺ T cells are a critical reservoir in chronic infections and cancer, yet the signals sustaining their cytokine production remain unclear. Here, we identify KLRF1 as part of a CD4-CD8 communication axis that supports cytokine production in late-differentiated human CD8⁺ T cells. KLRF1 is upregulated in late-differentiated CD8⁺ T cells, and neutralizing KLRF1 reduces TNF and IFN-γ production. Differentiated CD4⁺ T cells express the KLRF1 ligand AICL, and in co-culture only AICL⁺ - not AICL⁻ - CD4⁺ T cells enhance cytokine output in CD8⁺ T cells. Using spatial proteomics of lung adenocarcinoma and adjacent tissue, we found that CD4+ AICL⁺ and CD8+ KLRF1⁺ T cells are enriched and spatially interacting in non-tumor regions, whereas both populations are reduced within tumor tissue. Single-cell RNA-seq of tissue samples and scRNA/ATAC analyses of circulating immune cells further showed that CD8+KLRF1⁺ T cells display a Tpex-like transcriptional and chromatin-accessibility profile. Together, these data identify the AICL-KLRF1 axis as a CD4⁺-CD8⁺ communication pathway that supports cytokine competence in late-differentiated CD8⁺ T cells. |
| Source: | BioStudies |
| Publisher: | EMBL-EBI |
| Date: | 6 March 2026 |
| External Fulltext: | View full text on external repository or document server |
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