| Autor: |
Bullock ME; Department of Pathology and Cell Biology, Columbia University Irving Medical Center, 630 West 168th Street, New York, NY 10032, USA., Hogan T; Institute of Immunity and Transplantation, Division of Infection and Immunity, UCL, Royal Free Hospital, Rowland Hill Street, London NW3 2PF, United Kingdom., Williams C; Institute of Immunity and Transplantation, Division of Infection and Immunity, UCL, Royal Free Hospital, Rowland Hill Street, London NW3 2PF, United Kingdom., Morris S; Department of Pathology and Cell Biology, Columbia University Irving Medical Center, 630 West 168th Street, New York, NY 10032, USA., Nowicka M; Department of Pathology and Cell Biology, Columbia University Irving Medical Center, 630 West 168th Street, New York, NY 10032, USA., Sharjeel M; Institute of Immunity and Transplantation, Division of Infection and Immunity, UCL, Royal Free Hospital, Rowland Hill Street, London NW3 2PF, United Kingdom., van Dorp C; Department of Pathology and Cell Biology, Columbia University Irving Medical Center, 630 West 168th Street, New York, NY 10032, USA., Yates AJ; Department of Pathology and Cell Biology, Columbia University Irving Medical Center, 630 West 168th Street, New York, NY 10032, USA., Seddon B; Institute of Immunity and Transplantation, Division of Infection and Immunity, UCL, Royal Free Hospital, Rowland Hill Street, London NW3 2PF, United Kingdom. |
| Abstrakt: |
Quantifying the kinetics with which memory T cell populations are generated and maintained is essential for identifying the determinants of the duration of immunity. The quality and persistence of circulating CD4 + effector memory (T EM ) and central memory (T CM ) T cells in mice appear to shift with age, but it is unclear whether these changes are driven by the aging host environment, by cell age effects, or both. Here we address these issues by combining DNA labelling methods, established fate-mapping systems, a novel reporter mouse strain, and mathematical models. Together, these allow us to quantify the dynamics of both young and established circulating memory CD4 + T cell subsets, within both young and old mice. We show that that these cells and their descendents become more persistent the longer they reside within the T CM and T EM pools. This behaviour may limit memory CD4 T cell diversity by skewing TCR repertoires towards clones generated early in life, but may also compensate for functional defects in new memory cells generated in old age. |
