| First Author | Parsa R | Year | 2026 |
| Journal | Nat Immunol | Volume | 27 |
| Issue | 4 | Pages | 725-737 |
| PubMed ID | 41786978 | Mgi Jnum | J:393363 |
| Mgi Id | MGI:8328796 | Doi | 10.1038/s41590-026-02451-4 |
| Citation | Parsa R, et al. (2026) Tissue-specific clonal selection and differentiation of CD4(+) T cells during infection. Nat Immunol 27(4):725-737 |
| abstractText | Pathogen-specific CD4(+) T cells expand and contract during infection, generating memory clones that shape subsequent immune responses. How distinct tissue environments influence differentiation and clonal selection of polyclonal T cells remains unclear. Here we develop Tracking Recently Activated Cell Kinetics (TRACK) mice, a dual-recombinase fate-mapping system enabling the spatial and temporal labeling of recently activated CD4(+) T cells. Using TRACK mice during influenza infection, we observed organ-specific transcriptional differentiation and clonal selection in lung, mediastinal lymph nodes (medLNs) and spleen. During the effector phase, spleen-derived CD4(+) T cells adopted a stem-like migratory phenotype, whereas medLN-activated cells differentiated into T follicular helper cells. T cell receptor sequencing showed low clonal overlap between tissues during the effector response, consistent with distinct antigenic landscapes. During memory formation, overlap increased between lung- and medLN-derived cells, while splenic clones retained a distinct repertoire. These findings define tissue-dependent mechanisms that shape CD4(+) T cell fate and clonal architecture. |
