Journal
BIOLOGY OPEN
Volume 3, Issue 11, Pages 1071-1082Publisher
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/bio.201410173
Keywords
autoimmunity; AIRE; Aire(+) cell lines; central self-tolerance; thymic crosstalk
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Funding
- Japan Society for the Promotion of Science (JSPS)
- Ministry of Education, Culture, Sports, Science and Technology (MEXT)
- 21st Century COE Program
- Global COE Program at Keio University
- Toagosei Company Limited, Japan
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We previously established three mouse cell lines (Aire(+)TEC1, Aire(+)TEC2 and Aire(+)DC) from the medullary thymic epithelial cells (mTECs) and dendritic cells (mDCs). These cells constitutively expressed autoimmune regulator (Aire) gene'' and they exhibited various features of self antigen-presenting cells (self-APCs) present in the thymic medullary region. Here, we confirmed our previous observation that Aire(+) thymic epithelial cells adhere to fresh thymocytes and kill them by inducing apoptosis, thus potentially reproducing in vitro some aspects of the negative selection of Tcells in vivo. In this system, a single Aire(+) cell appeared able to kill similar to 30 thymocytes within 24 hrs. Moreover, we observed that ectopic expression of peripheral tissue-specific antigens (TSAs), and expression of several surface markers involved in mTEC development, increased as Aire(+) cell density increases toward confluency. Thus, these Aire(+) cells appear to behave like differentiating mTECs as if they pass through the developmental stages from intermediate state toward mature state. Surprisingly, an in vitro co-culture system consisting of Aire(+) cells and fractionated sub-populations of fresh thymocytes implied the possible existence of two distinct subtypes of thymocytes (named as CD4(+) killer and CD4(-) rescuer) that may determine the fate (dead or alive) of the differentiating Aire(+) mTECs. Thus, our in vitro co-culture system appears to mimic a part of in vivo thymic crosstalk''.
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