T-cell receptor sequencing reveals the clonal diversity and overlap of colonic effector and FOXP3+ T cells in ulcerative colitis.
T-cell receptor sequencing reveals the clonal diversity and overlap of colonic effector and FOXP3+ T cells in ulcerative colitis.
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DOI：
10.1097/mib.0000000000000242
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发表时间：
2015-01
影响因子：
4.9
通讯作者：
Carlson CS
中科院分区：
文献类型：
--
作者：
Lord J;Chen J;Thirlby RC;Sherwood AM;Carlson CS
FOXP3+ regulatory T cell (Tregs) prevent inflammation, but are paradoxically increased in ulcerative colitis (UC). Local T cell activation has been hypothesized to account for increased FOXP3 expression in colon lamina propria (LP) T cells. To see if human FOXP3+ LP T cells are an activated fraction of otherwise FOXP3− effector T cells (Teff) and explore their clonal diversity in health and disease, we deep sequenced clonally unique T cell receptor (TCR) hypervariable regions of FOXP3+ and FOXP3− CD4+ T cell subpopulations from inflamed versus non-inflamed colon LP or mesenteric lymph nodes (MLN) of patients with or without UC. The clonal diversity of each LP T cell population was no different between patients with versus without UC. Repertoire overlap was only seen between a minority of FOXP3+ and FOXP3− cells, including recently activated CD38+ cells and Th17-like CD161+ Teff, but this repertoire overlap was no different between patients with versus without UC, and was no larger than the overlap between Helios− and Helios+ FOXP3+ cells. Thus, at steady state, only a minority of FOXP3+, and particularly Helios+, T cells share a TCR sequence with FOXP3− effector populations in the colon LP, even in UC, revealing distinct clonal origins for LP Tregs and effector T cells in humans.
