The biology of lymphoid tissue inducer cells

Lymphoid tissue inducer (LTi) cells are a unique set of hematopoietic CD4+ IL-7Rα+ lineage- cells, which are required for the development of lymph nodes (LNs) and Peyer's patches (PPs) in mice. The differentiation of fetal liver (FL) progenitors into LTi cells is regulated by transcription factors and by cytokines provided by nonhematopoietic cells. During fetal development, LTi cells colonize the intestine and putative sites of LN formation, where they associate with vascular endothelial cells and mesenchymal stromal cells. They express a number of tumor necrosis factor super-family (TNFSF) members, amongst them lymphotoxin (LT) α1β2 engages LTβR expressed by stromal cells. Activation of the LTβR signaling pathway within stromal cells induces the NFκB-dependent transcription of genes that is required for the development of lymphoid tissues. LTβR signals also contribute to the formation of the splenic white pulp during fetal development. Fetal LTi cells not only migrate to putative primordia of secondary lymphoid organs, but also to the fetal thymus, where they are proposed to promote the differentiation of medullary thymic epithelial cells (mTECs). In adult mice, LTi cells persist in lymphoid organs and intestinal follicles, where they have a function in lymphoid tissue organization and adaptive immune responses.