Introduction: Selective interference with or enhancement of Treg function and/or migration are potentially therapeutically useful. However, to date the molecules which govern Treg migration seem to be the same as for conventional T cells. It is possible that differential expression levels, not expression of different molecules, may set Treg apart from effector and naÏve CD4 T cells. Here we tested the hypothesis that Treg express a unique combination of migration molecules compared to conventional T cells, and that this results in different molecular requirements for migration.
Methods: T cell subsets were generated using Foxp3GFP reporter mice, and flow purified based upon CD44, CD25, and Foxp3GFP expression. qRT-PCR quantitated gene expression. T cells were used in transmigration and time-lapse assays of movement on lymphatic endothelial SVEC4-10 cells or blood endothelial MS-1 cells.
Results: Treg expressed more Neuropilin-1, more CCR7 (the major lymph node homing chemokine receptor), more S1P1 (sphingosine 1-phosphate receptor 1, modulated by FTY720) than effector T cells; but less CCR7 and S1P1 than naÏve CD4 T cells by qRT-PCR. Treg also expressed intermediate levels of the transcription factor KLF2, known to be involved in control of CCR7 and S1P1, in comparison to naÏve and effector T cells. Treg expressed less total and high affinity LFA-1 by flow cytometry than effector cells in vitro, while in vivo resting Treg expressed similar levels of LFA-1 to naÏve CD4 T cells but less than effector/memory phenotype cells. In vitro generated natural and induced Treg (nTreg and iTreg) expressed similar levels of LFA-1. LFA-1 blockade reduced Treg but not effector T cell migratory speed and distance on a lymphatic endothelial cell line. In contrast, LFA-1 blockade did not alter Treg transmigration of lymphatic endothelium but did block naÏve and effector cell transmigration.
Conclusions: Treg express a distinct pattern of migratory molecules compared to both naÏve and effector CD4 T cells. Furthermore, Treg and non-Treg utilized LFA-1 differently in initial two-dimensional interactions with and transmigration across lymphatic endothelium. This indicates that while the migration-associated molecules expressed by Treg may be broadly the same as for conventional T cells, these molecules are not utilized identically. Thus, it is possible to differentially modulate Treg and effector T cell migration by blocking shared adhesion molecules which are utilized differently.
To cite this abstract in AMA style:Brinkman C, Bromberg J. Treg Express a Unique Pattern of Trafficking Molecules and Differentially Rely on LFA-1 for Migration Compared to Effector T Cells [abstract]. Am J Transplant. 2013; 13 (suppl 5). http://atcmeetingabstracts.com/abstract/treg-express-a-unique-pattern-of-trafficking-molecules-and-differentially-rely-on-lfa-1-for-migration-compared-to-effector-t-cells/. Accessed January 17, 2018.
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