Three distinct subsets of thymic epithelial cells in rats and mice defined by novel antibodies.

Yasushi Sawanobori,Chae Gyu Park,Motoyasu Satou,Christine D Dijkstra,Kenjiro Matsuno,Yusuke Kitazawa,Hiashi Ueta,Taishin Akiyama

doi:10.1371/journal.pone.0109995

Yasushi Sawanobori, Chae Gyu Park + Show 6 more

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https://doi.org/10.1371/journal.pone.0109995

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Abstract

AimThymic epithelial cells (TECs) are thought to play an essential role in T cell development and have been detected mainly in mice using lectin binding and antibodies to keratins. Our aim in the present study was to create a precise map of rat TECs using antibodies to putative markers and novel monoclonal antibodies (i.e., ED 18/19/21 and anti-CD205 antibodies) and compare it with a map from mouse counterparts and that of rat thymic dendritic cells.ResultsRat TECs were subdivided on the basis of phenotype into three subsets; ED18+ED19+/−keratin 5 (K5)+K8+CD205+ class II MHC (MHCII)+ cortical TECs (cTECs), ED18+ED21−K5−K8+ Ulex europaeus lectin 1 (UEA-1)+CD205− medullary TECs (mTEC1s), and ED18+ED21+K5+K8dullUEA-1−CD205− medullary TECs (mTEC2s). Thymic nurse cells were defined in cytosmears as an ED18+ED19+/−K5+K8+ subset of cTECs. mTEC1s preferentially expressed MHCII, claudin-3, claudin-4, and autoimmune regulator (AIRE). Use of ED18 and ED21 antibodies revealed three subsets of TECs in mice as well. We also detected two distinct TEC-free areas in the subcapsular cortex and in the medulla. Rat dendritic cells in the cortex were MHCII+CD103+ but negative for TEC markers, including CD205. Those in the medulla were MHCII+CD103+ and CD205+ cells were found only in the TEC-free area.ConclusionBoth rats and mice have three TEC subsets with similar phenotypes that can be identified using known markers and new monoclonal antibodies. These findings will facilitate further analysis of TEC subsets and DCs and help to define their roles in thymic selection and in pathological states such as autoimmune disorders.

Highlights

The thymus, a lymphoid organ with a lobular structure, is important for the development of T cells
Immunohistological profiles of Thymic epithelial cells (TECs) We first tested the reactivity of rat and mouse thymic sections with the newly developed ED18, ED19, ED21, and HD83 antibodies and a panel of antibodies specific to a selection of putative TEC antigens (Fig. 1)
CD205 was mostly coexpressed with the ED18 epitope in the cortex (Fig. S1), but not in the medulla. These results indicate that rat cortical TECs (cTECs) are ED18+ ED19+/2 keratin 5 (K5)+Keratin 8 (K8)+CD205+MHC class II (MHCII)+

Summary

Introduction

The thymus, a lymphoid organ with a lobular structure, is important for the development of T cells. Thymocytes (T cell precursors) are subjected to both negative and positive selection in the thymus. Thymocytes are subjected to positive selection, in which precursors with low reactivity to the MHC complex are deleted/eliminated. The thymocytes are subjected to negative selection in the medulla, a process that deletes/eliminates cells that have reactivity against self antigens [1]. Cortical and medullary TECs (cTECs and mTECs) can be distinguished by means of expression of certain keratins and specific cell-surface molecules, or selective binding of Ulex europaeus lectin 1 (UEA-1). Numerous studies have used these markers to describe the development or function of the thymus in mice, but few such studies have been conducted in other animals or in humans. The distribution and specificity of these markers in species other than mice remain largely unknown

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