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Citations to this article

Opposing chemokine gradients control human thymocyte migration in situ
Joanna Halkias, … , Astar Winoto, Ellen A. Robey
Joanna Halkias, … , Astar Winoto, Ellen A. Robey
Published April 15, 2013
Citation Information: J Clin Invest. 2013;123(5):2131-2142. https://doi.org/10.1172/JCI67175.
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Research Article Immunology Article has an altmetric score of 10

Opposing chemokine gradients control human thymocyte migration in situ

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Abstract

The ordered migration of thymocytes from the cortex to the medulla is critical for the appropriate selection of the mature T cell repertoire. Most studies of thymocyte migration rely on mouse models, but we know relatively little about how human thymocytes find their appropriate anatomical niches within the thymus. Moreover, the signals that retain CD4+CD8+ double-positive (DP) thymocytes in the cortex and prevent them from entering the medulla prior to positive selection have not been identified in mice or humans. Here, we examined the intrathymic migration of human thymocytes in both mouse and human thymic stroma and found that human thymocyte subsets localized appropriately to the cortex on mouse thymic stroma and that MHC-dependent interactions between human thymocytes and mouse stroma could maintain the activation and motility of DP cells. We also showed that CXCR4 was required to retain human DP thymocytes in the cortex, whereas CCR7 promoted migration of mature human thymocytes to the medulla. Thus, 2 opposing chemokine gradients control the migration of thymocytes from the cortex to the medulla. These findings point to significant interspecies conservation in thymocyte-stroma interactions and provide the first evidence that chemokines not only attract mature thymocytes to the medulla, but also play an active role in retaining DP thymocytes in the cortex prior to positive selection.

Authors

Joanna Halkias, Heather J. Melichar, Kayleigh T. Taylor, Jenny O. Ross, Bonnie Yen, Samantha B. Cooper, Astar Winoto, Ellen A. Robey

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Total citations by year

Year: 2025 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 Total
Citations: 1 6 3 1 2 3 4 3 3 7 4 2 39
Citation information
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Citations to this article (39)

Title and authors Publication Year
The Thymus as a Mirror of the Body's Gene Expression.
Passos GA, Genari AB, Assis AF, Monteleone-Cassiano AC, Donadi EA, Oliveira EH, Duarte MJ, Machado MV, Tanaka PP, Mascarenhas R
Advances in experimental medicine and biology 2025
Homeostatic cytokines reciprocally modulate the emergence of prenatal effector PLZF+CD4+ T cells in humans
Veronica Locher, Sara Park, Daniel Bunis, Stephanie Makredes, Trevor Burt, Gabriela Fragiadakis, Joanna Halkias
JCI Insight 2023
A Beginner's Guide to T Cell Development.
Bosselut R
Methods in molecular biology (Clifton, N.J.) 2023
Studying T Cell Development in Neonatal and Adult Thymic Slices.
McIntyre LL, Lutes LK, Robey EA
Methods in molecular biology (Clifton, N.J.) 2023
Multimodal human thymic profiling reveals trajectories and cellular milieu for T agonist selection
Heimli M, Flåm ST, Hjorthaug HS, Trinh D, Frisk M, Dumont KA, Ribarska T, Tekpli X, Saare M, Lie BA
Frontiers in immunology 2023
Severe CD8+ T lymphopenia in WHIM syndrome caused by selective sequestration in primary immune organs
Majumdar S, Pontejo SM, Jaiswal H, Gao JL, Salancy A, Stassenko E, Yamane H, McDermott DH, Balabanian K, Bachelerie F, Murphy PM
Journal of immunology (Baltimore, Md. : 1950) 2023
Thymocyte Development of Humanized Mice Is Promoted by Interactions with Human-Derived Antigen Presenting Cells upon Immunization.
Fukuhara T, Ueda Y, Lee SI, Odaka T, Nakajima S, Fujisawa JI, Okuma K, Naganuma M, Okazaki K, Kondo N, Kamioka Y, Matsumoto M, Kinashi T
International journal of molecular sciences 2023
Modeling human T1D-associated autoimmune processes
M Khosravi-Maharlooei, R Madley, C Borsotti, L Ferreira, R Sharp, M Brehm, D Greiner, A Parent, M Anderson, M Sykes, R Creusot
Molecular Metabolism 2022
Multi-objective optimization reveals time- and dose-dependent inflammatory cytokine-mediated regulation of human stem cell derived T-cell development
J Edgar, Y Michaels, P Zandstra
npj Regenerative Medicine 2022
How Thymocyte Deletion in the Cortex May Curtail Antigen-Specific T-Regulatory Cell Development in the Medulla
Wang C, Daley SR
Frontiers in immunology 2022
Heparan sulfate is essential for thymus growth
HP Hsu, YT Chen, YY Chen, CY Lin, PY Chen, SY Liao, CC Lim, Y Yamaguchi, CL Hsu, IL Dzhagalov
The Journal of biological chemistry 2021
From stem cell to immune effector: how adhesion, migration, and polarity shape T-cell and natural killer cell lymphocyte development in vitro and in vivo
BJ Lee, EM Mace, Y Yamashita
Molecular biology of the cell 2020
Factors that influence the thymic selection of CD8αα intraepithelial lymphocytes
NS Kurd, A Hoover, J Yoon, BM Weist, L Lutes, SW Chan, EA Robey
Mucosal Immunology 2020
T Lymphocyte Development and Activation in Humanized Mouse Model
JY Lee, AR Han, DR Lee
DEVELOPMENT & REPRODUCTION 2019
E-protein–regulated expression of CXCR4 adheres preselection thymocytes to the thymic cortex
T Kadakia, X Tai, M Kruhlak, J Wisniewski, IY Hwang, S Roy, TI Guinter, A Alag, JH Kehrl, Y Zhuang, A Singer
Journal of Experimental Medicine 2019
A role for phagocytosis in inducing cell death during thymocyte negative selection
NS Kurd, LK Lutes, J Yoon, SW Chan, IL Dzhagalov, AR Hoover, EA Robey
eLife 2019
Chemotactic Cues for NOTCH1-Dependent Leukemia
E Piovan, V Tosello, A Amadori, P Zanovello
Frontiers in immunology 2018
Intrathymic Notch3 and CXCR4 combinatorial interplay facilitates T-cell leukemia propagation
F Ferrandino, G Bernardini, G Tsaouli, P Grazioli, AF Campese, C Noce, A Ciuffetta, A Vacca, ZM Besharat, D Bellavia, I Screpanti, MP Felli
Oncogene 2018
Indirect presentation in the thymus limits naive and regulatory T-cell differentiation by promoting deletion of self-reactive thymocytes
JY Yap, RC Wirasinha, A Chan, DR Howard, CC Goodnow, SR Daley
Immunology 2018
Chemokine-Mediated Choreography of Thymocyte Development and Selection
JN Lancaster, Y Li, LI Ehrlich
Trends in Immunology 2018
Update on Aire and thymic negative selection
GA Passos, CA Speck-Hernandez, AF Assis, DA Mendes-da-Cruz
Immunology 2017
Progressive Changes in CXCR4 Expression That Define Thymocyte Positive Selection Are Dispensable For Both Innate and Conventional αβT-cell Development
B Lucas, AJ White, SM Parnell, PM Henley, WE Jenkinson, G Anderson
Scientific Reports 2017
Acquisition of cell migration defines NK cell differentiation from hematopoietic stem cell precursors
BJ Lee, EM Mace, C Parent
Molecular biology of the cell 2017
T-cell selection in the thymus: a spatial and temporal perspective
N Kurd, EA Robey
Immunological Reviews 2016
MicroRNA-205 Maintains T Cell Development following Stress by Regulating Forkhead Box N1 and Selected Chemokines
AR Hoover, I Dozmorov, J MacLeod, Q Du, MT de la Morena, J Forbess, K Guleserian, OB Cleaver, NS van Oers
The Journal of biological chemistry 2016
Preparation and Applications of Organotypic Thymic Slice Cultures
A Sood, M Dong, HJ Melichar
Journal of visualized experiments : JoVE 2016
Development of a diverse human T-cell repertoire despite stringent restriction of hematopoietic clonality in the thymus
MH Brugman, AS Wiekmeijer, M Eggermond, I Wolvers-Tettero, AW Langerak, EF de Haas, LV Bystrykh, JJ van Rood, G Haan, WE Fibbe, FJ Staal
Proceedings of the National Academy of Sciences 2015
Conserved and divergent aspects of human T-cell development and migration in humanized mice
J Halkias, B Yen, KT Taylor, O Reinhartz, A Winoto, EA Robey, HJ Melichar
Immunology and Cell Biology 2015
Cellular imaging in rheumatic diseases
RA Benson, IB McInnes, JM Brewer, P Garside
Nature Reviews Rheumatology 2015
The Contribution of Chemokines and Migration to the Induction of Central Tolerance in the Thymus
Z Hu, JN Lancaster, LI Ehrlich
Frontiers in immunology 2015
Thymus medulla fosters generation of natural Treg cells, invariant γδ T cells, and invariant NKT cells: What we learn from intrathymic migration: Highlights
JE Cowan, WE Jenkinson, G Anderson
European Journal of Immunology 2015
Thymic regulatory T cell niche size is dictated by limiting IL-2 from antigen-bearing dendritic cells and feedback competition
BM Weist, N Kurd, J Boussier, SW Chan, EA Robey
Nature Immunology 2015
A timeline demarcating two waves of clonal deletion and Foxp3 upregulation during thymocyte development
DY Hu, JY Yap, RC Wirasinha, DR Howard, CC Goodnow, SR Daley
Immunology and Cell Biology 2015
Semaphorin 3F and Neuropilin-2 Control the Migration of Human T-Cell Precursors
DA Mendes-da-Cruz, AC Brignier, V Asnafi, F Baleydier, CV Messias, Y Lepelletier, N Bedjaoui, A Renand, S Smaniotto, D Canioni, P Milpied, K Balabanian, P Bousso, S Leprêtre, Y Bertrand, H Dombret, N Ifrah, M Dardenne, E Macintyre, W Savino, O Hermine
PloS one 2014
Tracking migration during human T cell development
J Halkias, HJ Melichar, KT Taylor, EA Robey
Cellular and Molecular Life Sciences 2014
Distinct phases in the positive selection of CD8+ T cells distinguished by intrathymic migration and T-cell receptor signaling patterns
JO Ross, HJ Melichar, BB Au-Yeung, P Herzmark, A Weiss, EA Robey
Proceedings of the National Academy of Sciences 2014
Stable Interactions and Sustained TCR Signaling Characterize Thymocyte-Thymocyte Interactions that Support Negative Selection
HJ Melichar, JO Ross, KT Taylor, EA Robey
Journal of immunology (Baltimore, Md. : 1950) 2014
Plxnd1 expression in thymocytes regulates their intrathymic migration while that in thymic endothelium impacts medullary topology
YI Choi, JS Duke-Cohan, J Tan, J Gui, MK Singh, JA Epstein, EL Reinherz
Frontiers in immunology 2013
Distinct Temporal Patterns of T Cell Receptor Signaling During Positive Versus Negative Selection in Situ
HJ Melichar, JO Ross, P Herzmark, KA Hogquist, EA Robey
Science signaling 2013

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