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Immunol Cell Biol. 2019 May 25. doi: 10.1111/imcb.12276. [Epub ahead of print]

Regulatory T cells differ from conventional CD4+ T cells in their recirculatory behavior and lymph node transit times.

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Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Department of Physiology, Department of Microbiology and Immunology, McGill Research Centre for Complex Traits, McGill University, Montreal, QC, Canada.
Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
The Angie Fowler AYA Cancer Institute, UH Rainbow Babies & Children's Hospital, Cleveland, OH, USA.
Institute of Pathology, Charité University, Berlin, Germany.


Regulatory T cells (Tregs) continuously suppress autoreactive immune responses within tissues to prevent autoimmunity, yet the recirculatory behavior of Tregs between and within tissues enabling the maintenance of peripheral tolerance remains incompletely defined. Here, we quantified homing efficiency to and the dwell time of Tregs within secondary lymphoid organs (SLOs) and used intravital two-photon microscopy to measure Treg surveillance behavior of dendritic cells. Tregs homed substantially less efficiently to SLOs compared with conventional CD4+ T cells (Tconvs), despite similar expression of homing receptors. Tregs remained on average 2-3 times longer within the LN than Tconvs before exiting, and retained Tregs differed from recirculating Tregs in phenotype, motility and interaction duration with dendritic cells. Taken together, these data revealed fundamental differences in Treg versus conventional T cell in vivo recirculation and migration behaviors, identified a Treg population with prolonged LN dwell time, and provided quantitative insight into their spatiotemporal behavior within LNs.


Imaging the immune system; T cells; lymph node; regulatory T cells


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