Phenotypic and Functional Changes of Peripheral Ly6C(+) T Regulatory Cells Driven by Conventional Effector T Cells

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Title
Phenotypic and Functional Changes of Peripheral Ly6C(+) T Regulatory Cells Driven by Conventional Effector T Cells
Author(s)
Jun Young Lee; Juhee Kim; Jaeu Yi; Daeun Kim; Hee-Ok Kim; Daehee Han; Jonathan Sprent; You Jeong Lee; Charles D. Surh; Jae-Ho Cho
Publication Date
2018-03
Journal
FRONTIERS IN IMMUNOLOGY, v.9, no.437, pp.1 - 15
Publisher
FRONTIERS MEDIA SA
Abstract
A relatively high affinity/avidity of T cell receptor (TCR) recognition for self-peptide bound to major histocompatibility complex II (self-pMHC) ligands is a distinctive feature of CD4 T regulatory (Treg) cells, including their development in the thymus and maintenance of their suppressive functions in the periphery. Despite such high self-reactivity, however, all thymic-derived peripheral Treg populations are neither homogenous in their phenotype nor uniformly immune-suppressive in their function under steady state condition. We show here that based on the previously defined heterogeneity in the phenotype of peripheral Treg populations, Ly6C expression on Treg marks a lower degree of activation, proliferation, and differentiation status as well as functional incompetence. We also demonstrate that Ly6C expression on Treg in a steady state is either up-or downregulated depending on relative amounts of tonic TCR signals derived from its contacts with self-ligands. Interestingly, peripheral appearance and maintenance of these Ly6C-expressing Treg cells largely differed in an age-dependent manner, with their proportion being continuously increased from perinatal to young adult period but then being gradually declined with age. The reduction of Ly6C(+) Treg in the aged mice was not due to their augmented cell death but rather resulted from downregulation of Ly6C expression. The Ly6C down-regulation was accompanied by proliferation of Ly6C(+) Treg cells and subsequent change into Ly6C-effector Treg with concomitant restoration of immune-suppressive activity. Importantly, we found that this phenotypic and functional change of Ly6C(+) Treg is largely driven by conventional effector T cell population. Collectively, these findings suggest a potential cross-talk between peripheral Treg subsets and effector T cells and provides better understanding for Treg homeostasis and function on maintaining self-tolerance Copyright © 2018 Lee, Kim, Yi, Kim, Kim, Han, Sprent, Lee, Surh and Cho. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.ⓒ 2007 - 2018 Frontiers Media S.A. All Rights Reserved
URI
https://pr.ibs.re.kr/handle/8788114/4626
ISSN
1664-3224
Appears in Collections:
Academy of Immunology and Microbiology(면역 미생물 공생 연구단) > Journal Papers (저널논문)
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