Neuroendocrine influence on thymic haematopoiesis via the reticulo-epithelial cellular network.

The thymus provides an optimal cellular and humoral microenvironment for a cell line committed differentiation of haematopoietic stem cells. The immigration process requires the secretion of at least one peptide, called thymotaxin, by cells of the reticulo-epithelial (RE) network of the thymic stromal cellular microenvironment. The thymic RE cells are functionally specialised based on their intrathymic location and this differentiation is modulated by various interaction signals of differentiating Thymocytes and other nonlymphatic, haematopoietic stem cells. The subcapsular, endocrine, RE cell layer is comprised of cells filled with periodic acid Shiff's-positive granules, which also express A2B5/TE4 cell surface antigens and MHC Class I (HLA A, B, C) molecules. Thymic nurse cells also produce thymosins beta 3 and beta 4 and display a neuroendocrine cell specific immunophenotype (IP): Thy-1+, A2B5+, TT+, TE4+, UJ13/A+, UJ127.11+, UJ167.11+, UJ181.4+ and presence of common leukocyte antigen (CLA+). Cortical RE cells express a surface antigen, gp200-MR6, which plays a significant role of thymocyte differentiation. Medullar RE cells display MHC Class II (HLA-DP, HLA-DQ, HLA-DR) molecule restriction. Thymic RE cells also produce numerous cytokines that are important in various stages of haematopoietic cell activation and differentiation. The co-existence of pituitary hormone and neuropeptide secretion, as well as the production of a number of interleukins and growth factors, and expression of receptors for all, by RE cells is an unique molecular biological phenomenon. Thymic neuroendocrine polypeptides are the source of self antigens presented by the MHC molecules to differentiating haematopoietic stem cells. On the level of individual RE cells, the numerous projections associated with a single cell, which engulf developing lymphocytes, nurturing and guiding them in their maturation, may differ in their hormone production and/or hormone receptor expression profile, thus allowing a single cell to be involved in distinct, separate steps of the T-cell and other haematopoietic cell maturation process. Thymic RE cells represent an important cellular and humoural network within the thymic microenvironment and are involved in the homeopathic regulation mechanisms of the multicellular organism. The intrathymic T-lymphocyte selection is a complex, multistep process, influenced by several functionally specialised RE cells and under immuno-neuroendocrine regulation control reflecting the dynamic changes of the mammalian organism.