Tissue-resident memory CD4+ T cells are sustained by site-specific levels of self-renewal and continuous replacement
Tissue-resident memory T cells (TRM) protect from repeat infections within organs and barrier sites. The breadth and duration of such protection are defined at minimum by three quantities: the rate at which new TRM are generated from precursors, their rate of self-renewal, and their rate of loss thr...
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eLife Sciences Publications Ltd
2025-06-01
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| Online Access: | https://elifesciences.org/articles/104278 |
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| author | Jodie Chandler M Elise Bullock Arpit C Swain Cayman Williams Christiaan H van Dorp Benedict Seddon Andrew J Yates |
| author_facet | Jodie Chandler M Elise Bullock Arpit C Swain Cayman Williams Christiaan H van Dorp Benedict Seddon Andrew J Yates |
| author_sort | Jodie Chandler |
| collection | DOAJ |
| description | Tissue-resident memory T cells (TRM) protect from repeat infections within organs and barrier sites. The breadth and duration of such protection are defined at minimum by three quantities: the rate at which new TRM are generated from precursors, their rate of self-renewal, and their rate of loss through death, egress, or differentiation. Quantifying these processes individually is challenging. Here we combine genetic fate mapping tools and mathematical models to untangle these basic homeostatic properties of CD4+ TRM in the skin and gut lamina propria (LP) of healthy adult mice. We show that CD69+CD4+ TRM in skin reside for ∼24 days and self-renew more slowly, such that clones halve in size approximately every 5 weeks, and approximately 2% of cells are replaced daily from precursors. CD69+CD4+ TRM in LP have shorter residencies (∼14 days) and are maintained largely by immigration (4–6% per day). We also find evidence that the continuous replacement of CD69+CD4+ TRM at both sites derives from circulating effector-memory CD4+ T cells, in skin possibly via a local CD9− intermediate. Our approach maps the ontogeny of CD4+ TRM in skin and LP and exposes their dynamic and distinct behaviours, with continuous seeding and erosion potentially impacting the duration of immunity at these sites. |
| format | Article |
| id | doaj-art-81ba53268ae1457aa3e89766adff93a3 |
| institution | Kabale University |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
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| spelling | doaj-art-81ba53268ae1457aa3e89766adff93a32025-08-20T03:26:53ZengeLife Sciences Publications LtdeLife2050-084X2025-06-011410.7554/eLife.104278Tissue-resident memory CD4+ T cells are sustained by site-specific levels of self-renewal and continuous replacementJodie Chandler0M Elise Bullock1https://orcid.org/0000-0002-7876-4938Arpit C Swain2Cayman Williams3https://orcid.org/0000-0002-0518-1379Christiaan H van Dorp4https://orcid.org/0000-0002-7504-9947Benedict Seddon5https://orcid.org/0000-0003-4352-3373Andrew J Yates6https://orcid.org/0000-0003-4606-4483Institute of Immunity and Transplantation, Division of Infection and Immunity, UCL, Royal Free Hospital, London, United KingdomDepartment of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, United StatesDepartment of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, United StatesInstitute of Immunity and Transplantation, Division of Infection and Immunity, UCL, Royal Free Hospital, London, United KingdomDepartment of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, United StatesInstitute of Immunity and Transplantation, Division of Infection and Immunity, UCL, Royal Free Hospital, London, United KingdomDepartment of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, United StatesTissue-resident memory T cells (TRM) protect from repeat infections within organs and barrier sites. The breadth and duration of such protection are defined at minimum by three quantities: the rate at which new TRM are generated from precursors, their rate of self-renewal, and their rate of loss through death, egress, or differentiation. Quantifying these processes individually is challenging. Here we combine genetic fate mapping tools and mathematical models to untangle these basic homeostatic properties of CD4+ TRM in the skin and gut lamina propria (LP) of healthy adult mice. We show that CD69+CD4+ TRM in skin reside for ∼24 days and self-renew more slowly, such that clones halve in size approximately every 5 weeks, and approximately 2% of cells are replaced daily from precursors. CD69+CD4+ TRM in LP have shorter residencies (∼14 days) and are maintained largely by immigration (4–6% per day). We also find evidence that the continuous replacement of CD69+CD4+ TRM at both sites derives from circulating effector-memory CD4+ T cells, in skin possibly via a local CD9− intermediate. Our approach maps the ontogeny of CD4+ TRM in skin and LP and exposes their dynamic and distinct behaviours, with continuous seeding and erosion potentially impacting the duration of immunity at these sites.https://elifesciences.org/articles/104278tissue-resident memory T cellsmathematical modellingfate mapping |
| spellingShingle | Jodie Chandler M Elise Bullock Arpit C Swain Cayman Williams Christiaan H van Dorp Benedict Seddon Andrew J Yates Tissue-resident memory CD4+ T cells are sustained by site-specific levels of self-renewal and continuous replacement eLife tissue-resident memory T cells mathematical modelling fate mapping |
| title | Tissue-resident memory CD4+ T cells are sustained by site-specific levels of self-renewal and continuous replacement |
| title_full | Tissue-resident memory CD4+ T cells are sustained by site-specific levels of self-renewal and continuous replacement |
| title_fullStr | Tissue-resident memory CD4+ T cells are sustained by site-specific levels of self-renewal and continuous replacement |
| title_full_unstemmed | Tissue-resident memory CD4+ T cells are sustained by site-specific levels of self-renewal and continuous replacement |
| title_short | Tissue-resident memory CD4+ T cells are sustained by site-specific levels of self-renewal and continuous replacement |
| title_sort | tissue resident memory cd4 t cells are sustained by site specific levels of self renewal and continuous replacement |
| topic | tissue-resident memory T cells mathematical modelling fate mapping |
| url | https://elifesciences.org/articles/104278 |
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