Editors' ChoiceImmunology

T Cells Through the Age(s)

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Science Translational Medicine  17 Dec 2014:
Vol. 6, Issue 267, pp. 267ec215
DOI: 10.1126/scitranslmed.aaa3460

Most studies of healthy human immune cells, including T cells, are based on peripheral blood samples; however, immune cells are known to reside in or traffic to the bone marrow, lymph node basins, and tissues such as the lungs, gut, and skin. T cells in particular are complex cells which have varying states of differentiation that dictate their overall numbers, function, tissue localization, and types of memory subsets. Much of the research describing the T cell lineage and maintenance properties has been obtained from mouse models, but humans are more diverse and have longer natural life spans.

A recent study by Thome et al. characterized the T cells in blood, a variety of lymph node basins, and gut compartments in a large sample of normal human (organ) donors. In some ways, the most remarkable aspect of the study was the study population: 56 human subjects ranging in age from 3 years old to 73 years old, representing multiple races. The authors harvested viable T cells and characterized them with regard to CD4 and CD8 populations, naïve and memory subsets, diversity of repertoire, and markers of longevity and tissue retention. They found that most naïve and memory subsets (except one) were compartmentalized and that this pattern was consistent among diverse individuals. Also, certain subsets, such as naïve cells, underwent age-associated changes, but more so in lymphoid tissues than mucosal tissues. Next steps could include a deeper characterization of the bone marrow compartment and the chemokine receptor networking that dictates T cell homing.

As T cell therapies become an important therapeutic tool, we will need to gain a better understanding and map the fate of human T cells to fully exploit them as therapeutic agents. This study is a big step in that it prints the map of normal T cell distribution and function in normal donors through the human ages.

J. J. C. Thome et al., Spatial map of human T cell compartmentalization and maintenance over decades of life. Cell 159, 814–828 (2014). [Abstract]

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