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Cell. 2014 Nov 6;159(4):814-28. doi: 10.1016/j.cell.2014.10.026.

Spatial map of human T cell compartmentalization and maintenance over decades of life.

Author information

1
Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY 10032, USA; Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA.
2
Department of Surgery, Columbia University Medical Center, New York, NY 10032, USA.
3
Department of Systems Biology and Biomedical Informatics, and the JP Sulzberger Columbia Genome Center, Columbia University, New York, NY 10032, USA.
4
Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY 10032, USA.
5
The New York Organ Donor Network (NYODN), New York, NY 10001, USA.
6
Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY 10032, USA; Department of Surgery, Columbia University Medical Center, New York, NY 10032, USA; Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA. Electronic address: df2396@cumc.columbia.edu.

Abstract

Mechanisms for human memory T cell differentiation and maintenance have largely been inferred from studies of peripheral blood, though the majority of T cells are found in lymphoid and mucosal sites. We present here a multidimensional, quantitative analysis of human T cell compartmentalization and maintenance over six decades of life in blood, lymphoid, and mucosal tissues obtained from 56 individual organ donors. Our results reveal that the distribution and tissue residence of naive, central, and effector memory, and terminal effector subsets is contingent on both their differentiation state and tissue localization. Moreover, T cell homeostasis driven by cytokine or TCR-mediated signals is different in CD4+ or CD8+ T cell lineages, varies with their differentiation stage and tissue localization, and cannot be inferred from blood. Our data provide an unprecedented spatial and temporal map of human T cell compartmentalization and maintenance, supporting distinct pathways for human T cell fate determination and homeostasis.

PMID:
25417158
PMCID:
PMC4243051
DOI:
10.1016/j.cell.2014.10.026
[Indexed for MEDLINE]
Free PMC Article

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