tetano
Editor, Senior Moderator
Nat Immunol
. 2026 Mar 5.
doi: 10.1038/s41590-026-02451-4. Online ahead of print.
Tissue-specific clonal selection and differentiation of CD4⁺ T cells during infection
Roham Parsa[SUP] 1 2 [/SUP], Helder C Assis[SUP] 3 4 [/SUP], Tiago B R de Castro[SUP] 5 [/SUP], Gabriella Lima Dos Reis[SUP] 3 [/SUP], Arpita Sushil[SUP] 6 [/SUP], Harald Hartweger[SUP] 7 [/SUP], Angelina M Bilate[SUP] 3 [/SUP], Daniel Mucida[SUP] 8 9 [/SUP]
Affiliations
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.
. 2026 Mar 5.
doi: 10.1038/s41590-026-02451-4. Online ahead of print.
Tissue-specific clonal selection and differentiation of CD4⁺ T cells during infection
Roham Parsa[SUP] 1 2 [/SUP], Helder C Assis[SUP] 3 4 [/SUP], Tiago B R de Castro[SUP] 5 [/SUP], Gabriella Lima Dos Reis[SUP] 3 [/SUP], Arpita Sushil[SUP] 6 [/SUP], Harald Hartweger[SUP] 7 [/SUP], Angelina M Bilate[SUP] 3 [/SUP], Daniel Mucida[SUP] 8 9 [/SUP]
Affiliations
- PMID: 41786978
- DOI: 10.1038/s41590-026-02451-4
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.