Abstract
Promiscuous expression of tissue restricted antigens (TRAs) in medullary thymic epithelial cells (mTECs) is crucial for negative selection of self-reactive T cells to establish central tolerance. Intercellular transfer of self-peptide-MHC complexes from mTECs to thymic dendritic cells (DCs) allows DCs to acquire TRAs, which in turn contributes to negative selection and regulatory T cell generation. However, mTECs are unlikely to express all TRAs, such as immunoglobulins generated only in B cells after somatic recombination, hyper-mutation, or class-switches. We report here that both mTECs and cortical TECs can efficiently acquire not only cell surface but also intracellular proteins from thymocytes. This reveals a previously unappreciated intercellular sharing of molecules from thymocytes to TECs, which may broaden the TRA inventory in mTECs for establishing a full spectrum of central tolerance.
Highlights
Proper intrathymic T cell development ensures the generation of a repertoire of T cells against various pathogens and self-tolerant
We provide the first evidence that medullary thymic epithelial cells (mTECs) and cortical TECs (cTECs) are capable of acquisition of both cell surface and intracellular proteins from thymocytes
Because TCRα deficiency considerably decreased ZsGreen acquisition by thymic epithelial cells (TECs) from thymocytes, TCR-major histocompatibility complex (MHC) engagement-dependent mechanisms must be involved in intercellular protein transfer from thymocytes to TECs
Summary
Proper intrathymic T cell development ensures the generation of a repertoire of T cells against various pathogens and self-tolerant. The thymus is separated into the cortex and medulla, which are involved in the distinct function of the thymus with regard to T cell development [1,2,3]. Thymic progenitors enter the thymus at the conjunction between medulla and cortex. These cells, phenotypically CD4-CD8- double negative (DN), migrate toward the cortex to initiate early T cell development [4]. Expression of a functional αβ TCR on DP thymocytes and engagement of these TCRs with self-peptide major histocompatibility complex (MHC) expression on cortical TECs (cTECs) ensures their survival and differentiation to the CD4+CD8- and CD4-CD8+ single positive (SP) stage, known as positive selection.
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