The thymus microenvironment in regulating thymocyte differentiation

Abstract

The thymus plays a crucial role in the development of T lymphocytes by providing an inductive microenvironment in which committed progenitors undergo proliferation, T-cell receptor gene rearrangements and thymocyte differentiate into mature T cells. The thymus microenvironment forms a complex network of interaction that comprises non lymphoid cells (e.g., thymic epithelial cells, TEC), cytokines, chemokines, extracellular matrix elements (ECM), matrix metalloproteinases and other soluble proteins. The thymic epithelial meshwork is the major component of the thymic microenvironment, both morphologically and phenotypically limiting heterogeneous regions in thymic lobules and fulfilling an important role during specific stages of T-cell maturation. The process starts when bone marrow-derived lymphocyte precursors arrive at the outer cortical region of the thymic gland and begin to mature into functional T lymphocytes that will finally exit the thymus and populate the peripheral lymphoid organs. During their journey inside the thymus, thymocytes must interact with stromal cells (and their soluble products) and extracellular matrix proteins to receive appropriate signals for survival, proliferation and differentiation. The crucial components of the thymus microenvironment, and their complex interactions during the T-cell maturation process are summarized here with the objective of contributing to a better understanding of the function of the thymus, as well as assisting in the search for new therapeutic approaches to improve the immune response in various pathological conditions.

A novel aspect of the structure of the avian thymic medulla

“…Infection by human immunodeficiency virus (HIV) is followed by thymic involution and histological disintegration of the cortico-medullary border (Napolitano et al 2002). Similar experimental observations have been made after parasitic infection (Brito et al 2003;Gameiro et al 2010;Pérez et al 2012) and malnutrition (Savino et al 2007). These histological alterations are subsequently associated with increased subsceptibility to autoimmune disease and cancer development (Lynch et al 2009).…”

“…Therefore, the differentiation and/or plasticity of the marginal epithelial cells of the KPN are lost and the KNA is enlarged. Similar morphological events occur in mammals during age-related thymic involution, namely the expansion of the perivascular space (Gameiro et al 2010). Infection by human immunodeficiency virus (HIV) is followed by thymic involution and histological disintegration of the cortico-medullary border (Napolitano et al 2002).…”

“…The presence of reticular fibers at the corticomedullary border and in the inner medulla around the Hassall's bodies of human thymus has been shown by Yu and Lee (1993). The amount of reticular fibers and ECM components increases with age during physiological ) and acute (Lannes-Vieira et al 1991;Gameiro et al 2010) involutions. Our experimental results, in which acute involution was induced by DM, confirmed the increase of the ECM of the KNA.…”

Acute Thymic Involution and Mechanisms for Recovery

“…It is considered a primary immune organ in jawed vertebrates, in which it plays important roles in the selection, proliferation, development and differentiation of T cells and provides protection against infections by various pathogens (Bajoghli and Guo 2011;Gameiro et al 2010;Liu et al 2014). Despite its significance in immunity (Miller 2002;Samara et al 2016), the shrinkage of thymus that occurs with aging results in a decrease in tissue mass along with architectural alterations.…”

Growth hormone in the presence of laminin modulates interaction of human thymic epithelial cells and thymocytes in vitro

“…Thus, thymocytes adhere to these molecules, utilizing membrane receptors, and this adhesion is induced or impaired for various hormones [13]. …”