Cell types and cell signals important for normal thymic medullary epithelial cell development (HEM7P.231)

Abstract

Abstract Thymic crosstalk between medullary thymic epithelial cells (mTEC) and mature SP thymocytes is critical for tolerance in developing T cells as well as for mTEC development. Several TNF family receptor-ligand pairs, including RANK-RANKL, LTαβ-LTβR and CD40L-CD40, have been shown to be important in thymic crosstalk, in part via RelB mediated non-canonical NFκB pathway. Recently, we identified CD28-CD80/86 as an additional pathway important for mTEC development. CD80/86, LTβR, CD40, RANK, as well as MHCII (also shown to be important for mTEC development) are expressed by both mTEC and by bone marrow (BM) derived cells in the thymus. Thus, it is important to ask which cell types need to express these molecules in order to support mTEC development. To address the question, we have generated and analyzed BM chimeras or conditional knockout mice in which either non-BM-derived cells (including thymic epithelium) or BM-derived cells express the molecule in question. Interestingly, for CD40 and CD80/86, we find that expression on either non-BM or BM-derived cells is sufficient to promote mTEC development. For LTβR, and RANK, we find that expression on radiation-resistant non-BM derived cells is required. The ability of MHCII expression on specific cell populations to drive mTEC development is currently being examined. Our findings suggest that models of thymic crosstalk must consider not only communication between TEC and thymocytes but with other BM derived cell types as well.