Maintenance of Peripheral Naive T Cells Is Sustained by Thymus Output in Mice but Not Humans

被引:418
作者
den Braber, Ineke [1 ]
Mugwagwa, Tendai [2 ]
Vrisekoop, Nienke [1 ]
Westera, Liset [1 ]
Mogling, Ramona [1 ]
de Boer, Anne Bregje [1 ]
Willems, Neeltje [1 ]
Schrijver, Elise H. R. [1 ]
Spierenburg, Gerrit [1 ]
Gaiser, Koos [1 ]
Mul, Erik [3 ,4 ]
Otto, Sigrid A. [1 ]
Ruiter, An F. C. [5 ]
Ackermans, Mariette T. [5 ]
Miedema, Frank [1 ]
Borghans, Jose A. M. [1 ,2 ]
de Boer, Rob J. [2 ]
Tesselaar, Kiki [1 ]
机构
[1] Univ Med Ctr Utrecht, Dept Immunol, NL-3584 EA Utrecht, Netherlands
[2] Univ Utrecht, NL-3584 CA Utrecht, Netherlands
[3] Univ Amsterdam, Landsteiner Lab, NL-1066 CX Amsterdam, Netherlands
[4] Univ Amsterdam, Acad Med Ctr, NL-1066 CX Amsterdam, Netherlands
[5] Univ Amsterdam, Acad Med Ctr, Lab Endocrinol & Radiochem, NL-1105 AZ Amsterdam, Netherlands
关键词
EXCISION CIRCLE CONTENT; HIV-INFECTION; LIFE-SPAN; IN-VIVO; MARROW-TRANSPLANTATION; HUMAN ADULT; AGED MICE; LYMPHOCYTES; PROLIFERATION; REPERTOIRE;
D O I
10.1016/j.immuni.2012.02.006
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Parallels between T cell kinetics in mice and men have fueled the idea that a young mouse is a good model system for a young human, and an old mouse, for an elderly human. By combining in vivo kinetic labeling using deuterated water, thymectomy experiments, analysis of T cell receptor excision circles and CD31 expression, and mathematical modeling, we have quantified the contribution of thymus output and peripheral naive T cell division to the maintenance of T cells in mice and men. Aging affected naive T cell maintenance fundamentally differently in mice and men. Whereas the naive T cell pool in mice was almost exclusively sustained by thymus output throughout their lifetime, the maintenance of the adult human naive T cell pool occurred almost exclusively through peripheral T cell division. These findings put constraints on the extrapolation of insights into T cell dynamics from mouse to man and vice versa.
引用
收藏
页码:288 / 297
页数:10
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