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

Abstract

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.

The TCR assigns naive T cells to a preferred lymph node

“…Our results are also in agreement with a recent report based on sequencing “effector” T reg repertoires in another type of one-TCRα mice ( 29 ), which also reports reproducible differences in the TCRs used by CD4 T reg in different lymph nodes. Overall, these results suggest that CD4 T reg preferentially reside in lymph nodes in which their cognate self-antigens are presented, which, in turn, would be in agreement with their slower recirculation ( 30 , 31 ).…”

Immune-restoring CAR-T cells display antitumor activity and reverse immunosuppressive TME in a humanized ccRCC mouse model

“…Furthermore, comparison of the clonotypes found in CD4 + Treg and the other CD4 + T cell subsets using Jaccard coefficient revealed a lower similarity score in the G36-PDL1 group ( Figure S7 C). Since Treg can differentiate from conventional T cells, 55 and anti-PD-L1 mAb inhibits differentiation of induced Treg, 56 the lower Jaccard coefficient observed in G36-PDL1 indicates that the ICI payload changes TME conditions so they maintain active antitumor immunity but are unfavorable to support Treg differentiation.…”

A review on lymphocyte radiosensitivity and its impact on radiotherapy

“…In contrast to naïve adaptive lymphocytes which frequently migrate between secondary lymphoid organs, tissue-resident lymphocytes generally do not recirculate through the blood ( 177 ), but are also irradiated. The circulatory behavior of lymphocytes and their lymph node transit times also differs among lymphocytes subpopulations ( 178 , 179 ), e.g., CD4+ seem to recirculate more rapidly compared to CD8+. In addition, radiation likely affects lymphocyte migration, for instance, through radiation-induced changes in sphingosine-1-phosphate ( 180 ).…”