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Journal article
Human Lymph Nodes Maintain TCF-1(hi) Memory T Cells with High Functional Potential and Clonal Diversity throughout Life
The Journal of immunology (1950), v 201(7), pp 2132-2140
01 Oct 2018
PMID: 30111633
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Translating studies on T cell function and modulation from mouse models to humans requires extrapolating in vivo results on mouse T cell responses in lymphoid organs (spleen and lymph nodes [LN]) to human peripheral blood T cells. However, our understanding of T cell responses in human lymphoid sites and their relation to peripheral blood remains sparse. In this study, we used a unique human tissue resource to study human T cells in different anatomical compartments within individual donors and identify a subset of memory CD8(+) T cells in LN, which maintain a distinct differentiation and functional profile compared with memory CD8(+) T cells in blood, spleen, bone marrow, and lungs. Whole-transcriptome and high-dimensional cytometry by time-of-flight profiling reveals that LN memory CD8(+) T cells express signatures of quiescence and self-renewal compared with corresponding populations in blood, spleen, bone marrow, and lung. LN memory T cells exhibit a distinct transcriptional signature, including expression of stem cell-associated transcription factors TCF-1 and LEF-1, T follicular helper cell markers CXCR5 and CXCR4, and reduced expression of effector molecules. LN memory T cells display high homology to a subset of mouse CD8(+) T cells identified in chronic infection models that respond to checkpoint blockade immunotherapy. Functionally, human LN memory T cells exhibit increased proliferation to TCR-mediated stimulation and maintain higher TCR clonal diversity compared with memory T cells from blood and other sites. These findings establish human LN as reservoirs for memory T cells with high capacities for expansion and diverse recognition and important targets for immunotherapies.
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- Title
- Human Lymph Nodes Maintain TCF-1(hi) Memory T Cells with High Functional Potential and Clonal Diversity throughout Life
- Creators
- Michelle Miron - Columbia University Medical CenterBrahma V. Kumar - Columbia University Medical CenterWenzhao Meng - University of PennsylvaniaTomer Granot - Columbia University Medical CenterDustin J. Carpenter - Columbia University Medical CenterTakashi Senda - Columbia University Medical CenterDora Chen - University of PennsylvaniaAaron M. Rosenfeld - Drexel UniversityBochao Zhang - Drexel UniversityHarvey Lerner - LiveOnNY, New York, NY 10001.Amy L. Friedman - LiveOnNY, New York, NY 10001.Uri Hershberg - Drexel UniversityYufeng Shen - Columbia UniversityAdeeb Rahman - Icahn School of Medicine at Mount SinaiEline T. Luning Prak - University of PennsylvaniaDonna L. Farber - Columbia University Medical Center
- Publication Details
- The Journal of immunology (1950), v 201(7), pp 2132-2140
- Publisher
- American Association of Immunologists
- Number of pages
- 9
- Grant note
- S10OD020056 / OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA P01AI106697; U19AI128949 / National Institutes of Health (NIH); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA P30CA016520 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) U19AI128949 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) S10RR027050 / NATIONAL CENTER FOR RESEARCH RESOURCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR) TL1TR001875 / NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Advancing Translational Sciences (NCATS) T32AI06711; S10RR027050; S10OD020056 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000444804300031
- Scopus ID
- 2-s2.0-85053462652
- Other Identifier
- 991019167536704721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Immunology